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Abstract
The metabolism of radiolabelled alosetron was studied in rat, dog, rabbit, mouse and human. The metabolism in rat and dog was studied at a low and an elevated dose designed to generate sufficient quantities of metabolite for definitive identification. A strategy for the characterization of metabolites in cases of extensive metabolism was developed and demonstrated for alosetron. Semi–preparative high–performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC–MS), nuclear magnetic resonance (NMR) and liquid chromatography–nuclear magnetic resonance (HPLC–NMR) enabled the isolation and characterization of 28 metabolites of alosetron. The characterization of the metabolites in animal excreta facilitated the identification of human systemic metabolites.