Biosynthesis of Oxidative and Conjugated Metabolites of VRX-480773 and Identification of their Structures by LC-MS/MS and NMR

摘要

Two oxidative metabolites (M3 and M4), and glutathione (M1) and glucuronide (M2) conjugates of VRX-480773 were isolated following incubation with rat and human liver microsomes or S9 with cofactors. The isolated metabolites were pure based on UV trace (254 nm). The structures of four metabolites (M1, M2, M3, M4) were identified by LC-MS/MS and NMR. Authentic standard (M3) was prepared based on MS/MS and NMR data. 10-20 (mu)g of isolated metabolites were sufficient for 1D proton NMR analysis using 2.5 mm probe.