A sensitive assay of metoprolol and its major metabolite α-hydroxy metoprolol in human plasma and determination of dextromethorphan and its 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 human plasma samples obtained in in vitro-in vivo correlations (IVIVC) and bioavailability studies of extended release formulations of metoprolol tartrate. The metabolite, cr-hydroxy metoprolol (OH-met), could also be quantified. The analytes were extracted from the plasma using solid phase columns, separated on a C-4 analytical column followed by fluorimetric detection. The linearity, precision, accuracy, stability, selectivity 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. The same chromatographic conditions were slightly modified to quantify dextromethorphan and its metabolite dextrorphan in urine in the concentration 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.