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copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Loralie J Langman PhD DABCC (CC MD TC) F-ABFT Director Clinical and Forensic Toxicology Laboratory Mayo Clinic
Professor Mayo Clinic College of Medicine Rochester MN
September 30 2016
Urine Drug Screening The Essentials of Interpretation
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
DISCLOSURE
Relevant Financial Relationship(s) None
Off Label Usage None
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
50 y old male
Prescribed bull Percocet 5325
You want to see if he is taking it hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Testing
What specimen to collect
Is the individual impairedunder the influence now
Was an individual using or exposed to a drug
BLOOD SERUM
URINE
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
DISCLOSURE
Relevant Financial Relationship(s) None
Off Label Usage None
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
50 y old male
Prescribed bull Percocet 5325
You want to see if he is taking it hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Testing
What specimen to collect
Is the individual impairedunder the influence now
Was an individual using or exposed to a drug
BLOOD SERUM
URINE
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
50 y old male
Prescribed bull Percocet 5325
You want to see if he is taking it hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Testing
What specimen to collect
Is the individual impairedunder the influence now
Was an individual using or exposed to a drug
BLOOD SERUM
URINE
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Testing
What specimen to collect
Is the individual impairedunder the influence now
Was an individual using or exposed to a drug
BLOOD SERUM
URINE
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screening
How do we do what we do
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Traditional Drug Screening
Classically Two Stages
bull Stage 1 ndash Screen
bull Stage 2 ndash ConfirmationDefinitive Testing
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How do Immunoassay Screens work
Usually immunoassay-based method
Detect compounds that ldquolook likerdquo the drug you are testing for
Purpose is to identify negative samples
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Designed to look for illicit opiate use HEROIN rarr morphine
More practically thought of as a morphine immunoassay
Therefore detection of other opiates (ex codeine
hydrocodone hydromorphone oxycodone oxymorphone hellip) depends on antibody specificity
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
morphine oxycodone OH OHO
NCH3
O OO
NCH3
CH3
OH
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate Screening Immunoassay
Assay 1
Oxycodone ~ 20 cross reactivity bull Need ~ 5X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 1500 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Assay 2 Oxycodone ~ 3 cross reactivity bull Need ~ 33X more oxycodone to
give a positive Opiate Screen result than morphine
bull ~ 9900 ngmL oxycodone to give a positive screening test when a 300 ngmL cut-off is used
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines Presumptive Positive 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates negative 300
oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Identify what is causing the positive result in the immunoassay screening assay
OR
What to order when you are looking for a specific drug
May or may not be quantitative
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Laboratory Medicine Practice Guideline Using Clinical Laboratory Tests to Monitor Drug Therapy in Pain Management Patients Recommendation First-line definitive testing (qualitative or quantitative) is
recommended for detecting the use of relevant over-the-counter medications prescribed and non-prescribed drugs and illicit substances in pain management patients Definitive urine drug testing specifically identifies or quantifies a drug andor its metabolites
bull Strength of recommendation A bull Quality of evidence II
httpswwwaaccorgcommunitynational-academy-of-clinical-biochemistry
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Targeted Opioid Screen
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive Testing
Done in the Lab bull Gas Chromatography Mass Spectrometry
rsaquo (GCMS) bull Liquid Chromatography Mass Spectrometry
rsaquo (LCMS LCMS-MS TOF QTOF)
Pro bull Identify the drug(s)
Con
bull Looks for specific drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism
Phase 1 Reactions
Oxidation bull CYP450
Reduction
Phase 2 Reactions
Conjugation Reactions bull Glucuronidation bull Sulfate bull Glutathione bull Glucine bull Acetylation bull Methylation
Generally these reactions generate compounds that are more water soluble - aid in excretion
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism
Parent Drug MajorActive Metabolite (s) morphine codeine morphine heroin 6-mono-acetylmorphine morphine hydromorphone hydrocodone hydromorphone oxymorphone oxycodone oxymorphone
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73 Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Metabolism hellip and more
Parent Drug Minor metabolite
of parent drug
References
morphine hydromorphone lt25 Cone EJ et al J Anal Toxicol 2006 30(1) p 1-5
codeine hydrocodone lt11 Oyler JM et al J Anal Toxicol 2000 24(7) p 530-5
High doses for long period of time
Parent Drug Contaminant of parent drug
References
heroin codeine NOT metabolite
Very low levels compared to morphine
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 8th Edition Ed
2008 Chemical Toxicology Institute Foster City CA
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Acceptable Impurities in Commercial Drug Preparations Active Pharmaceutical Ingredient (API)
Process impurity ()
Allowable limit ()
Typical observed ()
hydrocodone codeine 015 000 ndash 010
hydromorphone morphine hydrocodone
015 010
000 ndash 0025 000 ndash 0025
morphine codeine 050 001 ndash 005
oxycodone hydrocodone 100 002 ndash 012
oxymorphone hydrocodone oxycodone
015 050
003 ndash 010 005 ndash 040
NOTE All contaminants when detected in greater amounts than the allowable limits stated above would be considered evidence of use These are NOT metabolites
Pesce A et al Interpretation of urine drug testing in pain patients Pain medicine 2012 13(7) p 868-85
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1
Opiate Confirmation (LC-MSMS)
Drug LOD
oxycodone 6600 ngmL 100 ngmL
oxymorphone 8152 ngmL 100 ngmL
morphine negative 100 ngmL
codeine negative 100 ngmL
hydrocodone 250 ngmL 38 100 ngmL
hydromorphone negative 100 ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 contrsquod
Patient is also prescribed Ritalin (methyl phenidate)
Urine Immunoassay Screen
Drug Result Cut-off (ngmL) amphetamines Presumptive Positive 500 barbiturates negative 200 benzodiazepines negative 200 cannabinoids negative 20 cocaine metabolite negative 150 opiates negative 300 oxycodone Presumptive Positive 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 1 cont
NH2
CH3 NH
O OH
amphetamine methylphenidate
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 9th Edition Ed 2011 Chemical Toxicology Institute Foster City CA Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th Ed 2011 McGraw-Hill
NHCH3
CH3
methamphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Screens are good a finding things you didnrsquot know you were looking for hellip Not good at finding things you are Whaaaaaaaaaaaaaat
Screening methods try to pick up as much as possible but to
do that you sacrifice of the detection limit and the ability to identify exactly which drug it is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
copyGetty images
Drug Screens
One could say that
drug screening is like looking for a needle in a haystack hellip
when you donrsquot know what the needle looks like or if there is a needle at all
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
If you know what you are looking for order a test that looks for it specifically (Definitive Testing)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
50 y old female
Prescribed bull methadone 60 mgd
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
Opiate
The term is often incorrectly used to refer to all drugs with morphine-like pharmacological action
More properly classified under the broader term opioid
httpdictionaryreferencecombrowseOpiate httpenwikipediaorgwikiOpiatecite_note-0
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiate vs Opioid
An opioid is a chemical substance that has a morphine-like action in the body
Natural opiates - alkaloids contained in the resin of the opium poppy bull morphine codeine hellip
Semi-synthetic opiates - created from the natural opiates
bull hydromorphone hydrocodone oxycodone oxymorphone diacetylmorphine (Heroin) hellip
Fully synthetic opioids bull fentanyl meperidine (pethidine) methadone tramadol hellip
Endogenous opioid peptides - produced naturally in the body
bull endorphins enkephalins dynorphins and endomorphins
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 12th ed New York McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opiates
O OHO
NCH3
CH3codeine
OH OO
NCH3
hydromorphone OH OO
NCH3
OH
oxymorphone
O OO
NCH3
CH3
OH
oxycodone O OO
NCH3
CH3hydrocodone
OH OHO
NCH3
morphine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Opioids in the Opiate assay
Opioids bull No ldquochemicalrdquo similarity to opiates
morphine OH OHO
NCH3
methadone
N
CH3
CH3
CH3
O CH3
fentanyl
N
N
CH3
O
tramadol
OCH3
NCH3 CH3
OH
meperidine
N
O
O
CH3
CH3
tapentadol
NCH3OH
CH3
CH3 CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2
Urine Immunoassay Screen
Drug Result Cut-off (ngmL)
amphetamines negative 500
barbiturates negative 200
benzodiazepines negative 200
cannabinoids negative 20
cocaine metabolite negative 150
opiates Presumptive Positive 300
oxycodone negative 100
methadone negative 300
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Case 2 cont hellip
Urine
Methadone Confirmation (GC-MS) Methadone 175 ngmL Screening assay cut off 300 ngmL
EDDP (methadone metabolite)
12062 ngmL
Confirmatory methods typically have limits of quantitation lower than the screening method
amp Why to order it when you know you are looking for it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methadone
Patients who are taking methadone for therapeutic purposes usually excrete both parent methadone and EDDP in their urine
BUT hellip
Methadone levels in urine are widely variable depending on factors such as dose timing of collection metabolism and urine pH (can even be undetectable)
EDDP levels in contrast are relatively unaffected by the influence of pH and are therefore preferable for assessing compliance with therapy
bull measure levels of both methadone and EDDP
Principles of Forensic Toxicology 2nd ed Washington DC AACC Press 2003
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another complicated class of drugs hellip
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepines
General Structure
N
N
Cl
OCH3
diazepam
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine Drug Phase I Phase II Lorazepam glucuronidation clonazepam 7-amino-clonzaepam glucuronidation Flunitrazepam 7-amino-flunitrazepam glucuronidation
Triazolam Hydroxy-traizolam glucuronidation Alprazolam Hydroxy-alprazolam glucuronidation Midazolam Hydroxy-midazolam glucuronidation Flurazepam Hydrox-fluazepam glucuronidation
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Drug Metabolism Benzodiazepine
Chlordiazepoxide Demoxepam
Diazepam
glucuronidation
Nordiazepam
Temazepam Oxazepam
EXCRETION
glucuronidation
oxidation CYP450
oxidation CYP450
oxidation CYP450
Baselt RC Disposition of Toxic Drugs and Chemicals in Man 7th Edition Ed 2005 Chemical Toxicology Institute Foster City CA Boerner U The metabolism of morphine and heroin in man Drug Metab Rev 1975 4(1) p 39-73
Goodman amp Gilmans The Pharmacological Basis of Therapeutics 10th Ed 2001 McGraw-Hill
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Benzodiazepine Immunoassay
The cross-reactivity of the different manufactures immunoassays to the over 30 prescribed benzodiazepines are even more variable than the opiates one
bull Clonazepam cross-reactivity is almost universally poor
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Tip
If you are looking for a specific drug hellip
Tell us
bull The more information the lab has the better
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Definitive methods hellip
Identify the drug(s) indicated with certainty hellip
So can those results be false positives too
But you just said they were definitive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
False Positives
Clinical False Positive Methodological False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamines
Amphetamine and methamphetamine have limited legitimate pharmacological uses including narcolepsy obesity and attention-deficit hyperactivity disorders
There are also prescription drugs that are metabolised to amphetamine or methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Logan BK Forensic Sci Rev 2002 14(p133-151
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Clinical False Positive
Drug uses Metabolites Adderall amphetamine ADHD Dexedrin d-amphetamine Narcolepsy
ADHD Desoxyn methamphetamine ADHD
amphetamine
Deprenyl selegiline Parkinsonrsquos Disease
methamphetamine amphetamine
Geowdin famprofazone Analgesic antipyretic
methamphetamine amphetamine
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
A thorough review of medical history to determine what medications the patient is prescribed
Canrsquot rule out they DIDNrsquoT use amphetamine or
methamphetamine
But does explain a positive test
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Point to Remember
An awareness of the patients completerecent medication history is critical to prevent the individual from being wrongly accused of using illicit drugs
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methodological False Positive
A drug is confirmedidentified when the drug is absent
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Amphetamine Type Stimulants cont
Amphetamine-type stimulants are often chiral compounds
Generally bullS(+) enantiomers stimulate the central nervous system bullR(-) enantiomers act peripherally
Illicit amphetamine-type stimulants are mixtures of S(-) and
R(-) enantiomers
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC
CH3
NH2
H H
NH2
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
CNS effects of S(+) methamphetamine [d-methamphetamine] are ~ 10X greater
Vasoconstrictive effects of R(minus) methamphetamine [l-methamphetamine] are greater
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
NHCH3
CH3
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Methamphetamine
Because of the minimal CNS activity and therefore low abuse potential R(minus) methamphetamine [l-methamphetamine] was included in some nonprescription nasal decongestants because of its vasoconstrictive properties
They have largely been replaced with other decongestant medications
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9
Hornbeck CL et al J Anal Toxicol 1993 17(1) p 23-5 Poklis A et al Ther Drug Monit 1995 17(1) p 89-94
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Some prescription drugs either have chiral amphetamine or methamphetamine as the active ingredient or are metabolised to chiral methamphetamine or amphetamine Drug Drugs detected
Dexedrin d-amphetamine S(+) amphetamine Deprenyl selegiline R(-) methamphetamine
R(-) amphetamine Vyvanse lisdexamfetamine
( L-lysine-dextroamphetamine) S(+) amphetamine
Logan BK Forensic Sci Rev 2002 14 p 133-151 Romberg RW et al J Forensic Sci 1995 40(6) p 1100-2
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
How to approach the casehellip
Routine confirmatory testing does not distinguish between the enantiomers
Chiral discrimination of methamphetamine isomers may be
necessary to distinguish
bull use of nonprescription nasal inhalants bull chiral prescription medications
from illicit use of methamphetamine
Principles of Forensic Toxicology 2nd Ed 2003 p 245-264 AACC Press Washington DC Cody JT J Chromatogr 1992 580(1-2) p 77-95
Fitzgerald RL et al J Anal Toxicol 1988 12(5) p 255-9 Hughes RO et al J Anal Toxicol 1991 15(5) p 256-9
Rasmussen LB et al J Chromatogr B Analyt Technol Biomed Life Sci 2006 842(2) p 136-41
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Urine Concentrations Levels in urine vary widely depending on factors such as
bull dose bull hydration status bull timing of collection bull metabolism bull hellip
CANNOT relate a urine concentration back to a dose
But within a given patient the pattern is may be ldquostablerdquo
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
| 3000 | 50 | 60 | |||
| 4500 | 90 | 50 | |||
| 2000 | 363636363636 | 55 | |||
| 3489 | 87225 | 40 | |||
| 4321 | 960222222222 | 45 | |||
| 6500 | 1083333333333 | 60 | |||
| 3583 | 7166 | 50 | |||
| 2679 | 487090909091 | 55 | |||
| 2965 | 456153846154 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 500 | 142857142857 | 35 | |||
| 4084 | 907555555556 | 45 | |||
| 3925 | 603846153846 | 65 | |||
| 400 | 75 | 53333333333 | |||
| 327 | 60 | 545 | |||
| 4598 | 707384615385 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 3579 | 7158 | 50 | |||
| 4084 | 742545454545 | 55 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drug ngmL creatinine gdL
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
| 3000 | 50 | 60 | |||
| 4500 | 90 | 50 | |||
| 2000 | 363636363636 | 55 | |||
| 3489 | 87225 | 40 | |||
| 4321 | 960222222222 | 45 | |||
| 6500 | 1083333333333 | 60 | |||
| 3583 | 7166 | 50 | |||
| 2679 | 487090909091 | 55 | |||
| 2965 | 456153846154 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 500 | 142857142857 | 35 | |||
| 4084 | 907555555556 | 45 | |||
| 3925 | 603846153846 | 65 | |||
| 400 | 75 | 53333333333 | |||
| 327 | 60 | 545 | |||
| 4598 | 707384615385 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 3579 | 7158 | 50 | |||
| 4084 | 742545454545 | 55 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Another way to look at urine results
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
sample
drugcreatinine
What this tells you is that something changed bull Disease bull Concomitant medications bull Altered compliance bull
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
| 3000 | 50 | 60 | |||
| 4500 | 90 | 50 | |||
| 2000 | 363636363636 | 55 | |||
| 3489 | 87225 | 40 | |||
| 4321 | 960222222222 | 45 | |||
| 6500 | 1083333333333 | 60 | |||
| 3583 | 7166 | 50 | |||
| 2679 | 487090909091 | 55 | |||
| 2965 | 456153846154 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 500 | 142857142857 | 35 | |||
| 4084 | 907555555556 | 45 | |||
| 3925 | 603846153846 | 65 | |||
| 400 | 75 | 53333333333 | |||
| 327 | 60 | 545 | |||
| 4598 | 707384615385 | 65 | |||
| 4328 | 961777777778 | 45 | |||
| 3579 | 5965 | 60 | |||
| 3579 | 7158 | 50 | |||
| 4084 | 742545454545 | 55 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
| sample | EDDP | creat | ratio | ||||
| 1 | 3000 | 500 | 600 | ||||
| 2 | 4500 | 900 | 500 | ||||
| 3 | 2000 | 364 | 550 | ||||
| 4 | 3489 | 872 | 400 | ||||
| 5 | 4321 | 960 | 450 | ||||
| 6 | 6500 | 1083 | 600 | ||||
| 7 | 3583 | 717 | 500 | ||||
| 8 | 2679 | 487 | 550 | ||||
| 9 | 2965 | 456 | 650 | ||||
| 10 | 4328 | 962 | 450 | ||||
| 11 | 3579 | 597 | 600 | ||||
| 12 | 500 | 143 | 350 | ||||
| 13 | 4084 | 908 | 450 | ||||
| 14 | 3925 | 604 | 650 | ||||
| 15 | 400 | 750 | 53 | ||||
| 16 | 327 | 600 | 55 | ||||
| 17 | 4598 | 707 | 650 | ||||
| 18 | 4328 | 962 | 450 | ||||
| 19 | 3579 | 597 | 600 | ||||
| 20 | 3579 | 716 | 500 | ||||
| 21 | 4084 | 743 | 550 |
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
The Key to understanding and interpreting drugs screens is
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Know what the lab can detect and let them know what you need
Drug screen interpretation requires two-way communication
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
A positive result bull They were exposed to the drug(s) identified bull Cant tell the dose or when it was taken
A negative result
bull Doesnrsquot exclude the possibility they were exposed to drug(s)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
The lab can tell you what active drug(s) was taken NOT the formulation
The lab CANNOT test for diversion bull We can help identify if a patient has not taken the drug bull but we canrsquot tell you what else the patient did with it
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Is the right test ordered
bull Be specific in what you order ndash you will only get what you ask for
bull Reminder
rsaquo Opiate vs opioids
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Relating a urine drug concentration to dose is difficult because
bull kidneyrsquos concentrating ability bull hydration of patient bull timing of collection (in relation to dose) bull hellip
Intuitively higher levels ~ recent use andor large dose
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Points to Take Home
Are any additional tests required
bull Do you require creatinine or specific gravity bull Do you require additional tests to screen for adulterants
rsaquo pH oxidants
bull Do you require Chain of Custody
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
langmanloraliemayoedu
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Focus on urine drug testing (UDT)
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Stimulants
Substance Period of Detection Amphetamine 1-3 days Methamphetamine 1-3 days Amphetamine variants (MDA MDMA)
1-3 days
Cocaine (benzyolecgonine) 1-4 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Opioids and Morphine Derivatives
Substance Period of Detection Morphine 1-3 days Codeine 1-3 days Oxycodone 1-3 days Methadone and metabolite (EDDP)
1 day - 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Alcohol 6-10 hours Barbiturates
Short acting 1 day Intermediate acting 2-3 days
Long acting 7-10 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Depressants
Substance Period of Detection Benzodiazepines
Short acting 1 day Intermediate acting 2-4 days
Long acting 1 week
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection LSD 8 hours Mescaline 2-3 days Phencyclidine 2-8 days Psilocybin 8 hours Amphetamine variants DOB DOM MDA MDMA
1-3 days
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
Department of Laboratory Medicine and Pathology copy 2010 Mayo Foundation for Medical Education and Research All Rights Reserved
Interpretation Detection Times Hallucinogens
Substance Period of Detection Marijuana
Single use 1-3 days Several times a week 2 weeks
daily 3-6 weeks
wwwnidanihgov
These are approximate detection times for the drug or metabolites in urine The actual detection time depends on individual metabolism and the dose of the drug
