Embed Size (px)
Citation preview
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 1/30
PART – I
Laboratory ErrorsPharma Uptoday
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 2/30
Error is the difference between the true result (or
accepted true result) and the measured result. If the error in an analysis is large, serious
consequences may result.
A patient may undergo expensive and even
dangerous medical treatment based on an incorrectlaboratory result may implement costly and incorrectmodifications to a plant or process because of ananalytical error.
ERROR
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 3/30
There are two principal types of error in analysis
determinate or systematic error
indeterminate or random error
Types of Errors
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 4/30
Determinate errors are caused by faults in the
analytical procedure or the instruments used in theanalysis.
The name determinate error implies that the cause ofthis type of error may be found out and then either
avoided or corrected. Determinate errors are systematic errors; that is, they
are not random.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 5/30
A particular determinate error may cause the
analytical results produced by the method to bealways too high;
Another determinate error may render all results toolow.
Sometimes the error is constant; All results are too high (or too low) by the same
amount.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 6/30
Sometimes the determinate error is proportional to
the true result, giving rise to proportional errors. Other determinate errors may be variable in both sign
and magnitude, such as the change in the volume of asolution as the temperature changes. Although this
variation can be positive or negative, it can beidentified and accounted for.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 7/30
Determinate errors can be additive or they can be
multiplicative. It depends on the error and how itenters into the calculation of the final result.
This determinate error could be the result of anincorrectly calibrated balance.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 8/30
If the balance is set so that the zero point is actually 0.5 mg
too high, all masses determined with this balance will be0.5 mg too high.
If this balance was used to weigh any standard solutionused in the laboratory, the standard concentration will beerroneously high, and all of the results obtained using this
standard will be erroneously low. The error is reported as the absolute error , the absolute
value of the difference between the true and measuredvalues.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 9/30
Determinate errors arise from some faulty step in the
analytical process. The faulty step is repeated every time the
determination is performed. Whether a sample isanalyzed 5 times or 50 times, the results may all agreewith each other (good precision) but differ widelyfrom the true answer (poor accuracy).
Although the replicate results are close to each other,that tells us nothing about their accuracy.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 10/30
Systematic error is under the control of the analyst. It is the analyst’s
responsibility to recognize and correct for these systematic errors that causeresults to be biased, that is, offset in the average measured value from thetrue value.
How are determinate errors identified and corrected?
Two methods are commonly used to identify the existence of systematicerrors.
One is to analyze the sample by a completely different analytical procedurethat is known to involve no systematic errors. Such methods are often called“standard methods”; they have been evaluated extensively by manylaboratories and shown to be accurate and precise.
If the results from the two analytical methods agree, it is reasonable toassume that both analytical procedures are free of determinate errors.
The second method is to run several analyses of a reference material ofknown, accepted concentration of analyte. The difference between theknown (true) concentration and that measured by analysis should reveal theerror. If the results of analysis of a known reference standard areconsistently high (or consistently low), then a determinate error is involvedin the method.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 11/30
The cause of the error must be identified and eithereliminated or controlled if the analytical procedure is togive accurate results.
Many clinical and analytical laboratories participate inproficiency testing programs, where “unknown” standard samples are sent to the laboratory on a regularbasis.
The results of these samples are sent to the government
or professional agency running the program. Theunknowns are of course known to the agency that sentthe test samples; the laboratory receives a report on theaccuracy and precision of its performance.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 12/30
Determinate errors can arise from uncalibrated
balances, improperly calibrated volumetric flasks orpipettes, malfunctioning instrumentation, impurechemicals, incorrect analytical procedures ortechniques, and analyst error.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 13/30
Analyst error : The person performing the analysis causesthese errors.
They may be the result of inexperience, insufficienttraining, or being “in a hurry”.
An analyst may use the instrument incorrectly,
perhaps by placing the sample in the instrument incorrectlyeach time.
Setting the instrument to the wrong conditions for analysis.
Consistently misreading a meniscus in a volumetric flask ashigh (or low)
Improper use of pipettes, such as “blowing out” the liquidfrom a volumetric pipette.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 14/30
Operational and personal errors These are due to factors for which the individual analyst is responsible
and are not connected with the method or procedure: they form part ofthe 'personal equation' of an observer.
The errors are mostly physical in nature and occur when sound analyticaltechnique is not followed.
Examples are: mechanical loss of materials in various steps of an analysis underwashing or overwashing of precipitates ignition of precipitates at incorrect temperatures insufficient cooling of crucibles before weighing allowing hygroscopic materials to absorb moisture before or during
weighing use of reagents containing harmful impurities.
Some analysts are unable to judge colour changes sharply in visualtitrations, which may result in a slight overstepping of the end point.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 15/30
Some other analyst-related errors are
Carelessness, which is not as common as is generallybelieved
Transcription errors, that is, copying the wrong
information into a lab notebook or onto a label
Calculation errors.
Proper training, experience, and attention to detail onthe part of the analyst can correct these types of
errors.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 16/30
Reagents and instrumentation:
Contaminated or decomposed reagents can causedeterminate errors.
Impurities in the reagents may interfere with thedetermination of the analyte, especially at the ppmlevel or below.
Prepared reagents may also be improperly labeled.
The suspect reagent may be tested for purity using aknown procedure or the analysis should be redoneusing a different set of reagents and the resultscompared.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 17/30
Numerous errors involving instrumentation are possible, including faulty construction of balances, use of uncalibrated or improperly calibrated weights, incorrect instrument alignment, incorrect wavelength settings, incorrect reading of values, and incorrect settings of the readout (i.e., zero signal should read zero). Any variation in proper instrument settings can lead to errors.
These problems can be eliminated by a systematic procedure tocheck the instrument settings and operation before use. Such
procedures are called standard operating procedures (SOPs) inmany labs. There should be a written SOP for each instrument and each
analytical method used in the laboratory.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 18/30
In instrumental analysis, electrical line voltage fluctuations area particular problem. This is especially true for automatedinstruments running unattended overnight.
Instruments are often calibrated during the day, when
electrical power is in high demand. At night, when power demand is lower, line voltage may
increase substantially, completely changing the relationshipbetween concentration of analyte and measured signal.
Regulated power supplies are highly recommended foranalytical instruments. The procedure for unattended analysisshould include sufficient calibration checks during theanalytical run to identify such problems.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 19/30
Analytical method
The most serious errors are those in the method itself. Examples of method errors include
incorrect sampling incomplete reaction for chemical methods, unexpected interferences from the sample itself or reagents used
having the analyte in the wrong oxidation state for the measurement loss of analyte during sample preparation by volatilization or precipitation an error in calculation based on incorrect assumptions in the procedure
(errors can evolve from assignment of an incorrect formula or molecularweight to the sample).
In titrimetric analysis errors may occur
owing to failure of reactions to proceed to completion, occurrence of induced and side reactions, reaction of substances other than the constituent being determined, difference between the observed end point and the stoichiometric
equivalence point of a reaction.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 20/30
Contamination
Contamination of samples by external sources can be aserious source of error and may be extremely variable.
Aluminum levels in the dust in a normal laboratory are so
high that dust prohibits the determination of low ppb levelsof aluminum in samples.
A special dust-free “clean lab” or “clean bench” with a filterto remove small dust particles may be required, fordetermination of traces of aluminum, silicon, and other
common elements such as iron. When trace (< ppm level) or ultratrace (< ppb level) organic
and inorganic analysis is required, the laboratoryenvironment can be a significant source of contamination.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 21/30
Contamination
Another major source of contamination in an analysis can be theanalyst. It depends on what kind of analytes are being measured, butwhen trace or ultratrace levels of elements or molecules are beingdetermined, the analyst can be a part of the analytical problem.
Many personal care items, such as hand creams, shampoos, powders,
and cosmetics, contain significant amounts of chemicals that may beanalytes. The problem can be severe for volatile organic compounds in
aftershave, perfume, and many other scented products and forsilicone polymers, used in many health and beauty products.
Powdered gloves may contain a variety of trace elements and should
not be used by analysts performing trace element determinations.Hair, skin, and clothing can shed cells or fibers that can contaminate asample.
Determinate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 22/30
Indeterminate errors are not constant or biased.
They are random in nature and are the cause of slightvariations in results of replicate samples made by the sameanalyst under the same conditions.
Sources of random error include the limitations of readingbalances, scales such as rulers or dials, and electrical “noise” ininstruments. For example, a balance that is capable of
measuring only to 0.001 g cannot distinguish between twosamples with masses of 1.0151 and 1.0149 g. In one case themeasured mass is low, in the other case it is high.
Indeterminate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 23/30
Indeterminate errors are not constant or biased.
They are random in nature and are the cause of slightvariations in results of replicate samples made by the sameanalyst under the same conditions.
Sources of random error include the limitations of readingbalances, scales such as rulers or dials, and electrical “noise” in instruments. For example, a balance that is capable of
measuring only to 0.001 g cannot distinguish between twosamples with masses of 1.0151 and 1.0149 g. In one case themeasured mass is low, in the other case it is high.
Indeterminate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 24/30
These random errors cause variation in results, some of which maybe too high and some too low.
The average of the replicate determinations is accurate, but eachindividual determination may vary slightly from the true value.
Indeterminate errors arise from sources that cannot be corrected,avoided, or even identified, in some cases.
All analytical procedures are subject to indeterminate error.
However, because indeterminate error is random, the errors will
follow a random distribution. This distribution can be understood using the laws of probability
and basic statistics. The extent of indeterminate error can becalculated mathematically.
Indeterminate Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 25/30
Gross errors differ from indeterminate and determinate errors.They usually occur only occasionally, are often large, and may causea result to be either high or low.
They are often the product of human errors.
For example,
if part of a precipitate is lost before weighing, analytical results will below.
Touching a weighing bottle with your fingers after its empty mass is
determined will cause a high mass reading for a solid weighed in thecontaminated bottle.
Gross errors lead to outliers, results that appear to differ markedlyfrom all other data in a set of replicate measurements.
Gross Error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 26/30
An absolute error is the numerical difference between ameasured value and a true or accepted value.
A relative error is the absolute error divided by the true oraccepted value.
Absolute & Relative errors
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 27/30
Concentration errors
Labeling errors
Calculation errors Manual calculation
Using wrong formula
Computational calculation Using wrong formula in excel
Using different location (wrong cell) in the excel sheet Improper use of $, () symbols.
Rounding off errors
Common identified error
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 28/30
When a set of replicate results is obtained it may be the case thatone of the results appears to be “out of line”; such a result is calledan outlier .
While it is tempting to discard data that does not “look good” inorder to make the analysis seem more precise, it is never a goodpractice unless there is justification for discarding the result.
If it is known that an error was made, such as spillage of the sample, use of the wrong size pipet, incorrect dilution, or
allowing the sample to boil to dryness when it should not have done so, the result should be rejected and not used in any compilation of
results. In practice, if something of this sort is suspected, a good analyst will
discard the sample and start over if possible.
Rejection of Results
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 29/30
PART – II
UNDERSTAND THE IMPORTANCE
OF EACH STEP TO MINIMISEERRORS
7/22/2019 Laboratory Errors in Analytical Laboratory
http://slidepdf.com/reader/full/laboratory-errors-in-analytical-laboratory 30/30
Text book of Quantitative Chemical Analysis- 5th Edition –Vogel.
Pharmaceutical Analysis : A Textbook for Pharmacy Students &Pharmaceutical Chemists – David G. Watson
Handbook of instrumental techniques for analytical chemistry –
Frank Settle. Instant Notes in Analytical Chemistry – D. Kealey & P.J. Haines.
Analytical Chemistry for Technicians 3rd edition (CRC, 2003) – Kenkel.
pharmaceutical-drug-analysis book 2nd edition – Ashutoshkar.
Fundamentals of Analytical Chemistry 8th edition HQ (Thomson,2004) – Douglas A. Skoog.
Undergraduate instrumental analysis 6th edition – James W.Robinson.
References
