Determining metabolism differences in rats and dogs for a novel anti-viral compound: The use of a LTQ-XL linear ion trap to detect 21 metabolites in a single injection.

摘要

1A was rapidly converted to 2A. The main metabolite detected in dog plasma and liver was mono-oxidation of the propyl side chain (M-K), mono-oxidation of the di-fluorophenyl ring (M-L) and mono-oxidation in the core of the molecule (M-Y). Metabolite M-L and M-Y have a potential to form a reactive intermediate arene oxide which could bind to proteins. Metabolites M-E, M-H, M-L, M-V and M-Y were detected in greater amounts in dog than in rat. Intermediates of these metabolites could be an arene oxide and could be the reactive intermediate responsible for hepatotoxicity. The rapid scan speed of the Thermo LTQ-XL is sufficient enough to detect at least 21 metabolites in one injection.