Lawrence A. Pachla

Bioanalytic Considerations for Pharmacokinetic and Biopharmaceutic Studies

The correct evaluation of pharmacokinetic and biopharmaceutic data can only be achieved if accurate analytic data are obtained. The accuracy of analytic data depends on the criteria used to validate the method. Consequently, careful scrutiny of drug stability, assay sensitivity, selectivity, recovery, linearity, precision, and accuracy is necessary for the proper interpretation of data. The importance of method validation and its influence on pharmacokinetic and biopharmaceutic data evaluation and interpretation will be discussed.

A validated liquid chromatographic method for the antiallergy agent CI-922 in dog and rat plasma.

A sensitive, specific and rapid liquid chromatographic procedure to selectively monitor CI-922 in dog and rat plasma was developed and validated. Plasma samples were acidified and extracted with ethyl ether. The organic layer was evaporated to dryness, reconstituted with mobile phase, and the analytes were separated and quantified on an octadecylsilane stationary phase (lambda = 340 nm). The procedure was linear from 0.05 to 3.0 mug ml(-1) with a detection limit of 0.02 mug ml(-1). The accuracy of the method had relative errors of 7.6, 4.2 and 5.4% for dog plasma controls containing 0.5, 1.50 and 2.5 mug CI-922 ml(-1), respectively. The corresponding precision was 5.0, 4.0 and 4.8% (RSD). Similarly, relative standard deviations less than 4.6% and relative errors of less than 1.4% were obtained for rat plasma controls. The method is suitable for pharmacology, toxicology and pharmacokinetic studies of CI-922.

Liquid chromatographic analysis of the adenosine agonist PD 117519 in dog plasma

PD 117519 (I) [(R)-iV-(2,3-dihydro-lH-inden1-yl)adenosine, CI-9471 is an adenosine agonist which has shown oral antihypertensive activity in pharmacological animal models [l, 21. Physicochemical properties of this compound include an aqueous solubility of 0.21 mg ml-‘, a p& value of 2.4 (in 50% methanol), and an apparent octanol-water partition coefficient (log P) of 1.99 at pH 7. A sensitive and selective assay was required to quantitate PD 117519 in dog plasma to support pre-clinical pharmacokinetic studies.