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International Guidelines for Bioanalytical Method Validation: A Comparison and Discussion on Current Scenario


US FDA released guidelines for bioanalytical method validation in 2001 and it became the basis for guidelines such as ANVISA and EMA. Even though there is a general agreement between these guidelines in terms of evaluation of validation parameters, significant diversity exists with respect to methodology employed. Present review compares and summarizes the regulatory guidelines issued by US FDA, ANVISA and EMA for bioanalytical method validation. This review also discusses evaluation of certain validation parameters such as matrix effect, incurred sample reanalysis, various stability aspects, effect of anticoagulant counter ions, specificity in the presence of concomitant medications, and identification of pharmacokinetic repeats wherein specific guidance and general consensus amongst scientific community does not exist.

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American Association of Pharmaceutical Scientists


The National Health Surveillance Agency


Calibration curve


Coefficient of variation


Calibration and validation group


Detection limit


Design of experimentation


Ethylenediaminetetraacetic acid


European Medicines Agency


Good Laboratory Practices


Higher quality control sample


Internal Standard


Incurred Sample Reanalysis


Limit of detection


Limit of quantification


Lower limit of quantification


Quality control sample at lower limit of quantification


Matrix factor


Middle quality control sample


Quality control sample


Residual standard deviation


Upper limit of quantification


United States Food and Drug Administration


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Correspondence to Jyoti Paliwal.

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Kollipara, S., Bende, G., Agarwal, N. et al. International Guidelines for Bioanalytical Method Validation: A Comparison and Discussion on Current Scenario. Chromatographia 73, 201–217 (2011).

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  • Bioanalysis
  • Validation
  • US FDA
  • EMA
  • Regulatory guidance