04-12-2012, 01:32 PM
Analytical Method Validation Definition and Protocol
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Specificity
Ability of an analytical method to measure the analyte free from interference due to other components.
Specificity: Related Terms
Selectivity
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Bias
Used in USP to describe specificity (Degree of bias)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
the sample without added substances
Specificity: ICH/USP
An investigation of specificity should be conducted during the validation of an identification test, an impurities assay, and a potency assay.
Procedures used will depend on the intended objective of the analytical procedure.
If a method can not completely discriminate, two of more procedures are recommended.
ICH Specificity: Identification
Should be able to discriminate between compounds closely related in structure.
Confirmed by obtaining negative results for samples with spiked related compounds and positive results for samples with analyte.
Choice of potential interfering substances should be based on sensible scientific judgment considering substances that could likely occur.
Specificity: Potential Interference
Placebo
Drug Substance Degradants
Drug Product Degradants
Related Substances
Packaging Extractables
Range: USP/ICH
The interval between the upper and lower concentrations of analyte in the sample that have been demonstrate to have a suitable level of precision, accuracy, and linearity.
Accuracy: ICH/USP
Should be established across specified range of analytical procedure.
Should be assessed using a minimum of 3 concentration levels, each in triplicate (total of 9 determinations)
Should be reported as:
Percent recovery of known amount added or
The difference between the mean assay result and the accepted value
[attachment=42410]
Specificity
Ability of an analytical method to measure the analyte free from interference due to other components.
Specificity: Related Terms
Selectivity
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Bias
Used in USP to describe specificity (Degree of bias)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
the sample without added substances
Specificity: ICH/USP
An investigation of specificity should be conducted during the validation of an identification test, an impurities assay, and a potency assay.
Procedures used will depend on the intended objective of the analytical procedure.
If a method can not completely discriminate, two of more procedures are recommended.
ICH Specificity: Identification
Should be able to discriminate between compounds closely related in structure.
Confirmed by obtaining negative results for samples with spiked related compounds and positive results for samples with analyte.
Choice of potential interfering substances should be based on sensible scientific judgment considering substances that could likely occur.
Specificity: Potential Interference
Placebo
Drug Substance Degradants
Drug Product Degradants
Related Substances
Packaging Extractables
Range: USP/ICH
The interval between the upper and lower concentrations of analyte in the sample that have been demonstrate to have a suitable level of precision, accuracy, and linearity.
Accuracy: ICH/USP
Should be established across specified range of analytical procedure.
Should be assessed using a minimum of 3 concentration levels, each in triplicate (total of 9 determinations)
Should be reported as:
Percent recovery of known amount added or
The difference between the mean assay result and the accepted value