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Advion expression
Compact Single Quadrupole API
Mass Spectrometer
Lecture 7, Page 34
Cart-Based LC/MS: Move where you want it and plug it in.
Lecture 7, Page 35
Specifications
• Ion Source: ESI with APCI option (swapped with minimal effort)
• ASAP: Atmospheric Sample Analysis Probe employs APCI
• API: orthogonal ion sampling from heated capillary – allows small single turbo pump (Patents filed**)
• Analyzer: Quadrupole Mass filter
• Detector: Electron multiplier with dynode
• Flow rate range:10 µL/min to 1 mL/min
• Polarity: +ve and –ve ion in sequential analyses
• Mass Range: 10 – 2,000 amu (possible extension to 1,500)
• Scan Speed: 10,000 amu/sec (compatible with UPLC)
• Resolution: 0.5-0.7 Da (FWHM) at 1000 amu/sec over entire mass range
• Sensitivity: 25 ng reserpine injected on column, measured at 10:1 S/N with full scan 100 to 1000 amu (achieved 20 - 200 pg)
• Mass accuracy: 0.1 Da over entire mass range
• Mass stability: 0.1 Da over 30 day
Lecture 7, Page 36
Mass Resolution
10 pmol/uL infusion of Quaternary Amine Mix (major peaks are (M+H)+ ions)
Tetramethylammonium, 74.10 Tetrabutylammonium, 242.28 Tetradecylammonium, 578.55
Tetraoctadecylammonium, 1027.16
Lecture 7, Page 37
• Little or no sample preparation • No chromatography • Data in < 1 minute The closed end of a glass capillary is dipped into the sample of interest or scraped on a solid surface, and then placed into the CMS for analysis. Ideal for: • Reaction monitoring • Compound ID • Food safety • Natural products
ASAP® – Atmospheric Solids Analysis Probe
Lecture 7, Page 38
SPME Sample Preparation for Drugs in Urine
The Procedure
Lecture 7, Page 39
Oxycodone C18H21NO4 MW: 315.36
Codeine C18H21NO3 MW: 299.36
Morphine C17H19NO3 MW: 285.34
SPME sample procedure for three opiates in urine with (Fiber was LC tip C18) 1. SPME Tip was conditioned in MeOH for 5 minutes 2. Equilibrium in water was 10 minutes 3. Extraction time: 10 minutes (Immersed tip in sample where the sample was stirred by magnet stir
bar. 4. After extraction, the SPME fiber/sample was dried in air for 2 minutes 5. ASAP-SPME-MS analysis
Preparation of fortified urine sample Each compound was a stock solution at 1 mg/ml in methanol. A 50ul stock solution of each compound was spiked in 1.85 ml urine which made a fortified urine sample with 25 ng/ul of the three opiates.
Three Opiates: Sample preparation and SPME Extraction
Lecture 7, Page 40
Mass spectra of three opiates
ASAP-SPME-MS Analysis of Opiates in Urine (Codeine, Morphine and Oxycodone: 25ng/ul in Urine)
Total Ion Current
XIC for m/z 286,
Morphine [M+H]+
Oxycodone [M+H]+
Codeine [M+H]+ Morphine
[M+H-H2O]+
Lecture 7, Page 41
Extraction procedure for three opiates in urine with SPME (LC tip C18) 1. SPME Tip was conditioned in MeOH for 10 minutes 2. Equilibrium in water for 5 minutes 3. Extraction time: 5 and 15 minutes (Immersed tip in sample where the sample was stirred by
magnet stir bar. 4. After extraction, the SPME fiber was dried in air about 2 minutes 5. ASAP-SPME-MS analysis
Preparation of fortified urine sample The stock solution of testosterone was 1.0 mg/ml in methanol . A 25 ul of stock solution for of testosterone was spiked in 4.75 ml urine which made a fortified urine sample with 5 ng/ul of testosterone.
Testosterone: Sample preparation and SPME Extraction
Testosterone C19H28O2
MW: 288.2
Lecture 7, Page 42
ASAP-SPME-MS Analysis of 5ng/ul testosterone in urine Extract time: 15 mins
used tip after cutting off the black part
Mass spectrum of testosterone in urine
Extract ion current of the m/z 289
Total ion current
[M+H]+
Lecture 7, Page 43
Amlodipine in Urine
Amlodipine C20H25ClN2O5
MW: 408.87
Preparation of fortified urine sample The stock solution of amlodipine was 1.0 mg/ml in methanol by dissolving a 2.5 mg tablet in 2.5 mL Methanol. The 50ng/ul and 100ng/ul amlodipine in urine was made by spiking the stock solution in urine sample.
All the SPME fiber for amlodipine test was used without conditioning in solvent
Lecture 7, Page 44
ASAP-SPME-MS Analysis of 50 ng/ul Amlodipine in urine Extract time: 5 mins, SPME LC Tips SCX/C18
Mass spectrum of Amlodipine in urine
XIC for m/z 406
Total ion current
[M+H]+
C20H25ClN2O5
MW: 408.87
Lecture 7, Page 45
ASAP-SPME-MS of 50ng/ul Amlodipine in urine Extract time: 5 mins, SPME LC Tips C18
Lecture 7, Page 46
Jack Henion, Nigel Sousou, Advion, Inc.
and
Brian Musselman, IonSense, Inc.
Rapid Screening of ‘White Powders’ for Organic Compounds Using a DART-Equipped API Compact
and Transportable Mass Spectrometer.
Lecture 7, Page 47
Mass Spectrometry Experimental
• Expression Compact Mass Spectrometer (CMS) – Single quadrupole: mass range 10-1200 m/z units
• Full-scan or SIM – Does not provide EI, MS/MS or HRMS – Does provide molecular weight
– API inlet amenable to ESI, APCI, DART, etc. • Can do infusion, FIA, LC/MS, IC/MS, SFC/MS, TLC/MS
– Mass Spec fits in a hood or on a cart and is – transportable – Pos/Neg DART modes can be used – Sample introduction via porous swab
• Swab with sample is robotically introduced to ionization region
Lecture 7, Page 48
‘Meth-Labs’ Continue to be Found
• State police charge man, woman after discovering meth lab near Syracuse, NY
Lecture 7, Page 49
Methamphetamine in Baking Powder DART CMS
Methamphetamine Standard
2% Methamphamphetamine in Baking Powder
MW = 149
(M+H)+
Lecture 7, Page 50
Summary of Staged Meth Lab Scene ( Imagine this Situation)
• A Meth Lab is in the forrest a half-mile off the road next to an airstrip
• An airplane lands to pick up several kilos of fresh-made Meth as a white powder
– Aircraft are often used to quickly transport illegal drugs
• While quickly loading a box of Meth plastic bags into the airplane a plastic bag of Meth poweder is dropped on the ground
• The police have received a tip and rush to the scene
• The airplane quickly takes off as the police arrive
• The dropped bag of Meth is analyzed on-site by a transportable DART-compact MS system. – An example situation which demonstrates that simple, inexpensive mass spectrometry
can be taken to the sample rather than the sample taken to the lab!
• Let’s watch a video of this ‘pretend’ situation but with real on-site DART-CMS analysis of methamphetamine in a white powder.
Lecture 7, Page 51
Meth-Lab Drug Bust (Simulated) Video
Lecture 7, Page 52
Summary MS Miniaturization
• Transportability within the laboratory is possible
• Many applications do not require superlative performance
• Personal access to MS is desired but current costs are too high for personal systems
• Laboratory space is limited so smaller is better
• Ease-of-use MS would help be well received
• Low cost systems could be more prevalent
Lecture 7, Page 53
References
• Sassi, A. P.; Hooper, H. H., Making analysis in the life sciences faster through miniaturization. Am. Lab. 2000, 32 (October), 36-41.
• Gac, S. L.; Berg, A. v. d., Miniaturization and Mass Spectrometry. RSC Publishing: Cambridge CB4 0WF, UK, 2009; p 315.
• Chaudhary, A.; van Amerom, F. H. W.; Short, R. T.; Bhansali, S., Fabrication and testing of a miniature cylindrical ion trap mass spectrometer constructed from low temperature co-fired ceramics. International Journal of Mass Spectrometry 2006, 251 (1), 32-39.
• Lammert, S. A.; Rockwood, A. A.; Wang, M.; Lee, M. L.; Lee, E. D.; Tolley, S. E.; Oliphant, J. R.; Jones, J. L.; Waite, R. W., Miniature Toroidal Radio Frequency Ion Trap Mass Analyzer. Journal of the American Society for Mass Spectrometry 2006, 17 (7), 916-922.
• Janfelt, C.; Graesboll, R.; Lauritsen, F. R., Characterization and optimization of membrane inlets for a miniature ion trap mass spectrometer operating at a high background pressure of humid air. International Journal of Mass Spectrometry 2008, 276 (1), 17-23.
• Malcolm, A.; Wright, S.; Syms, R. R. A.; Dash, N.; Schwab, M.-A.; Finlay, A., Miniature Mass Spectrometer Systems Based on a Microengineered Quadrupole Filter. Analytical Chemistry 2010.
• Malcolm, A.; Wright, S.; Syms, R. R.; Moseley, R. W.; O'Prey, S.; Dash, N.; Pegus, A.; Crichton, E.; Hong, G.; Holmes, A. S.; Finlay, A.; Edwards, P.; Hamilton, S. E.; Welch, C. J., A miniature mass spectrometer for liquid chromatography applications. Rapid Commun Mass Spectrom 2011, 25 (21), 3281-8.
• Tadjimukhamedov, F. K.; Jackson, A. U.; Nazarov, E. G.; Ouyang, Z.; Cooks, R. G., Evaluation of a Differential Mobility Spectrometer/Miniature Mass Spectrometer System. Journal of the American Society for Mass Spectrometry 2010, 21 (9), 1477-1481.
Lecture 7, Page 54