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Analytical method validation (revision 3)

Old revision·05:45, 5 Aug 2024·ResinRhoswen

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Analytical method validation
Governing guidanceICH Q2(R2)
Core characteristicsSpecificity, linearity, range, accuracy, precision, detection and quantitation limits
EstablishesFitness for a stated purpose, not correctness in general
Analytical method infobox · conventions

Analytical method validation is the documented demonstration that an analytical procedure is suitable for its intended purpose. It is not a demonstration that a method is correct in the abstract: a method validated for assay of a drug substance is not thereby validated for detection of a trace impurity, and the purpose is part of the claim.[1]

The characteristics assessed are specificity, linearity, range, accuracy, precision (repeatability and intermediate precision), the detection and quantitation limits where relevant, and robustness. Which of these apply depends on what the method is for, and the compendial treatment of the same subject is framed the same way.[1][2]

The characteristics

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CharacteristicQuestion it answers
SpecificityDoes the method measure the analyte and not something else?
LinearityIs response proportional to concentration over the range?
RangeBetween what limits is the method demonstrated to work?
AccuracyDoes the result agree with the true value?
RepeatabilityDo replicate determinations agree within a run?
Intermediate precisionDo they agree across days, analysts and instruments?
Limit of detectionBelow what level is presence undetectable?
Quantitation limitBelow what level is a number unreliable?
RobustnessDoes the result survive small deliberate changes in conditions?

References

  1. ^ a b International Council for Harmonisation, Q2(R2): Validation of Analytical Procedures (2023).
  2. ^ United States Pharmacopeia, General Chapter <1225>, Validation of Compendial Procedures.