Metabolism of RS-0481, a New Host Mediated Antitumor Activator (1) : Identification of Metabolites in Rat and Dog

Abstract

Biotransformation of (4R)-3-benzoyl-N-[(1R)-1-phenylethyl]-4-thiazolidinecarboxamide (RS-0481), developed as a host mediated antitumor activator, was studied in rats and dogs. Twelve metabolites, M₁ to M₁₂, were isolated from urine, bile and plasma samples of rats or dogs after oral administration of RS-0481 or ¹⁴C-RS-0481 as a tracer. The structures of these metabolites were characterized by GC/EI/MS and ¹H-NMR, and were comfirmed by comparison with corresponding authentic standards. The applicabilities of LC/APCI/MS for the identification of metabolites and the plausible metabolic pathways in these animals involving stereospecific oxidation of RS-0481 were also discussed.