Validation and Control of Bioanalytical Methods

Abstract

The results of toxicokinetic, pharmacokinetic, and bioequivalence studies are used to make critical decisions regarding the safety and efficacy of anticancer drug substances. Therefore, measurement of anticancer drug concentrations in biological matrices is an important aspect in the development of these products. Such data are required by regulating agencies to support new drug applications as well as for line extensions and generic products of these drugs. It is therefore most essential to adequately characterize and fully validate the applied bioanalytical methods used in the determination of this class of compounds to ensure that they function in the manner in which they are intended. Since the release of the FDA prescribed Guidance for Industry in Bioanalytical Method Validation in May 2001, it is much clearer what is required for method validation. There are however a number of areas that are still not well developed in the FDA guidance, and the recently proposed draft European Medical Agency guidance addresses some of these. Apart from discussing acceptance criteria on the primary matrices required to determine bioanalytical assay suitability such as accuracy, precision, and selectivity, the draft guidance proposes additional criteria for other important aspects such stability tests, matrix effects, cross validation, and incurred sample reanalysis. The current chapter provides an overview of the current scientific approaches based on the literature while considering them in the context of these guidances in this highly regulated area.

Effects of Single-Nucleotide Polymorphisms of FMO3 and FMO6 Genes on Pharmacokinetic Characteristics of Sulindac Sulfide in Premature Labor

“…The interday precision was estimated from the analysis of the six standards on 5 separate days during the method validation. The intra-and interday precisions of sulindac sulfide were in the ranges of 2.9;10.6 and 6.3;9.0%, respectively, which was acceptable for all the quality control samples (Karnes et al, 1991).…”

Retrospective Data Analysis and Proposal of a Practical Acceptance Criterion for Inter-laboratory Cross-validation of Bioanalytical Methods Using Liquid Chromatography/Tandem Mass Spectrometry

“…1). When accuracy and precision were separately evaluated as those could independently affect the concentration data (14), it was indicated that the larger analytical biases of the cross-validation samples analyzed at the receiving laboratories were caused by neither the analytical variation nor analytical biases in the bioanalytical methods used at the receiving laboratories with assuming that the analytical variation of a bioanalytical method could be estimated from the CV of the cross-validation samples (Figs. 2 and 3).…”

High‐performance liquid chromatography quantification of enantiomers of a Dihydroxylated tetrahydrofuran natural product

“…Importantly, the precision of detection for both analytes was more than 85% and therefore within the interval set by the FDA concerning validation of bioanalytical methods. 29 Finally, the stability of stock solutions under storage conditions and the stability of extracted biological samples in the autosampler were tested and both (+)-and (−)-petromyroxol were stable for at least 1 month in the −20°C freezer and at least 48 hours in the 4°C autosampler (data not shown).…”