VALIDATION OF LIQUID-CHROMATOGRAPHIC AND GAS-CHROMATOGRAPHIC METHODS - APPLICATIONS TO PHARMACOKINETICS

Validations of analytical methods are important for the generation of data for bioavailability, bioequivalence and pharmacokinetic studies. It is essential to use well defined and fully validated analytical met hods to obtain reliable results that can be satisfactorily interpreted . This manuscript is intended to provide guiding principles for the ev aluation of a method's overall performance. For this purpose, all of t he variables of the method are considered, including sampling procedur e, sample preparation, chromatographic separation, detection and data evaluation. The criteria considered are as follows; stability, selecti vity, limits of quantification and of detection, accuracy, precision, linearity, recovery and ruggedness. Models used for analytical calibra tion curves are explained in term of validity and limitations, along w ith a presentation of the most common statistical considerations used to validate the model. Appropriate means of testing precision and accu racy, the most important factors in assessing method quality, are pres ented. Other issues, such as re-validation, cross-validation, partial sample volume, endogenous drugs and biological matrix of limited avail ability, are also discussed.