IDENTIFICATION OF HYDROXYLATED METABOLITE OF SFZ-47, A NOVEL ANTI-INFLAMMATORY AND ANALGESIC AGENT, AND ITS CONJUGATES IN RABBITS

AIM: To identify the metabolite of 3H-1,2-dihydro-2-(4-methyl-phenylamino) methyl-1-pyrrolizinone(SFZ-47), a novel anti-inflammatory and analgesic agent in rabbits. METHODS: Urine samples from 0 to 12 h were collected after single oral dose of 100 mg SFZ-47 to each of four rabbits. The urine samples with or without hydrolysis by β-glucuronidase/sulphatase were purified by SPE column (Sep-Pak C₁₈) and analyzed with LC/MSⁿ for potential metabolites. RESULTS: Hydroxylated metabolite of SFZ-47 and its conjugates of glucuronide and sulfate were first identified either by directly comparing the observed mass spectra and the chromatographic retention time with authentic substance or by the diagnostic ions in full scan MSⁿ (n=2,3) mode. CONCLUSION: According to the experimental results in this study, the major metabolic pathway of SFZ-47 in rabbits should be that the methyl group of SFZ-47 was oxidized to hydroxymethyl and then to carboxyl group, followed by conjugation with β-glucuronic acid or sulfuric acid.