DETERMINATION OF THE DIHYDROPYRIDINE ARYLOXYPROPANOLAMINE Z6568 AND ITS ACIDIC METABOLITES IN PLASMA, URINE AND TISSUES BY SOLID-PHASE EXTRACTION AND LIQUID-CHROMATOGRAPHY NEGATIVE-ION MASS-SPECTROMETRY

A sensitive and selective liquid chromatographic/mass spectrometric as say for the determination of the dihydropyridine aryloxypropanolamine compound Z6568 and its monoacidic metabolites in plasma, urine and tis sues has been developed and validated. Z6568 and the acidic metabolite s were isolated from the biological matrices by solid-phase extraction , separated by reversed-phase high-performance liquid chromatography a nd detected by mass spectrometry using a thermospray interface. Filame nt ionization and negative-ion detection were used, monitoring the mol ecular ion of Z6568 and a major fragment of the acidic metabolites. Th e analysis of spiked plasma, urine and tissues demonstrated good accur acy and precision of the assay with a detection limit of 0.5 ng ml(-1) for Z6568 and 2 ng ml(-1) for the metabolites. Data relative to the o ptimization of the extraction procedure, mass spectrometric conditions and the validation protocol are reported. The method was used to inve stigate the metabolic fate and tissue distribution in laboratory anima ls.