Simvastatin: In Vitro Metabolic Profiling of a Potent Competitive HMG-CoA Reductase Inhibitor

Simvastatin (SV) is a semisynthetic derivative of lovastatin (LV), which biosynthetically produced from the fungus Aspergillus terreus and has high log p value (log = 4.39)and thus hepatic extraction efficacy in controlling cholesterol synthesis. The current study was undertaken to investigate metabolic profile SV using various mass spectrometry (MS) platforms. Metabolic profiling studied vitro models, rat liver microsomes (RLMs), isolated perfused hepatocytes (RLHs) both ion trap triple quadruple LC–MS/MS systems. A total 29 metabolites were identified. Among them, three types SV-related phase-I metabolites, namely exomethylene simvastatin acid (exomethylene SVA), monohydroxy SVA, dihydrodiol identified as new RLMs. No phase-II while incubating with RLHs.