A SENSITIVE ASSAY OF METOPROLOL AND ITS MAJOR METABOLITE ALPHA-HYDROXY METOPROLOL IN HUMAN PLASMA AND DETERMINATION OF DEXTROMETHORPHAN ANDITS METABOLITE DEXTRORPHAN IN URINE WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND FLUOROMETRIC DETECTION

A reverse-phase High Performance Liquid Chromatographic (HPLC) method was developed for the analysis of metoprolol in the large number of hu man plasma samples obtained in in vitro-in vivo correlations (IVIVC) a nd bioavailability studies of extended release formulations of metopro lol tartrate. The metabolite, cr-hydroxy metoprolol (OH-met), could al so be quantified. The analytes were extracted from the plasma using so lid phase columns, separated on a C-4 analytical column followed by fl uorimetric detection. The linearity, precision, accuracy, stability, s electivity and ruggedness were validated for the concentration ranges of 1-400 ng ml(-1) for metoprolol and 0.5-200 ng ml(-1) for OH-met. Th e same chromatographic conditions were slightly modified to quantify d extromethorphan and its metabolite dextrorphan in urine in the concent ration range 0.052-0.05 mu g ml(-1) as a method for screening for fast metabolizers. (C) 1998 Elsevier Science B.V. All rights reserved.