DETERMINATION OF FELODIPINE, ITS ENANTIOMERS, AND A PYRIDINE METABOLITE IN HUMAN PLASMA BY CAPILLARY GAS-CHROMATOGRAPHY WITH MASS-SPECTROMETRIC DETECTION

Sensitive methods based on capillary gas chromatography (GC) with mass spectrometric (MS) detection in a selected-ion monitoring mode (SIM) for the determination of racemic felodipine, its enantiomers, and a py ridine metabolite in human plasma are described. Following liquid-liqu id extraction from plasma, enantiomers of felodipine were separated on a chiral HPLC column (Chiralcel OJ) and fractions containing each iso mer were collected on a continuous basis using a fraction collector. T hese fractions were later analyzed by GC-MS-SIM. A similar method base d on GC-MS-SIM detection was developed for the determination of racemi c felodipine and its pyridine metabolite with a minor modification of sample preparation. The limits of quantitation in plasma were 0.1 ng/m l for both the R(+)- and S(-)-enantiomers of felodipine and 0.5 ng/ml for both racemic felodipine and its pyridine metabolite. The stereosel ective assay was used to support a clinical study with racemic felodip ine, and was capable of analyzing more than 30 plasma samples per day.