SIMULTANEOUS MEASUREMENT OF DOLASETRON AND ITS MAJOR METABOLITE, MDL-74,156, IN HUMAN PLASMA AND URINE

A selective and sensitive analytical method for the simultaneous measu rement of dolasetron (I) and its major metabolite, MDL 74,156 (II), in human plasma and urine samples has been developed using a structural analogue, MDL 101,858, as internal standard (I.S.). The compounds were extracted from plasma and urine using solvent extraction after the ad dition of the I.S. Chromatographic separation was carried out on a rev ersed-phase HPLC column and detection and quantification was by fluore scence with excitation and emission wavelengths of 285 and 345 nm, res pectively. Linear responses were obtained over concentration ranges of 5 to 1000 pmol/ml for plasma samples and 20 to 1000 pmol/ml for urine samples with correlation coefficients for the calibration curves exce eding 0.999 in all cases. Intra-day and inter-day reproducibility yiel ded limits of quantification of 10 pmol/ml for I and 5 pmol/ml for II in plasma and 50 pmol/ml for I and II in urine. The method has been ap plied to the simultaneous analysis of both compounds in plasma and uri ne samples coming from clinical pharmacokinetic studies.