Characterization of fimasartan metabolites in human liver microsomes and human plasma

Abstract

1.The metabolites of fimasartan (FMS), a new angiotensin II receptor antagonist, were characterized in human liver microsomes (HLM) and human subjects.2.We developed a method for a simultaneous quantitative and qualitative analysis using predictive multiple reaction monitoring information-dependent acquisition-enhanced product ion scanning. To characterize metabolic reactions, FMS metabolites were analyzed using quadrupole-time of flight mass spectrometer in full-scan mode.3.The structures of metabolites were confirmed by comparison of chromatographic retention times and mass spectra with those of authentic metabolite standards.4.In the cofactor-dependent microsomal metabolism study, the half-lives of FMS were 56.7, 247.9 and 53.3min in the presence of NADPH, UDPGA and NADPH+UDPGA, respectively.5.The main metabolic routes in HLM were S-oxidation, oxidative desulfuration, n-butyl hydroxylation and N-glucuronidation.6.In humans orally administered with 120mg FMS daily for 7 days, the prominent metabolites were FMS S-oxide and FMS N-glucuronide in the 0-8-h pooled plasma sample of each subject.7.This study characterizes, for the first time, the metabolites of FMS in humans to provide information for its safe use in clinical medicine.