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