Biotransformation of NSAIDs by pig liver microsomes in vitro: Kinetics, metabolites identification and toxicity prediction

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used pharmaceuticals in animals. In the current study, the biotransformation of five NSAIDs by pig liver microsomes (PLMs) was studied. The pseudo-first-order kinetics mode was obtained for the metabolization of the studied NSAIDs by PLMs in vitro. The metabolites were identified by high performance liquid chromatography with a high-resolution LTQ-Orbitrap mass spectrometry. The hydroxylation of benzene was confirmed to be the dominating metabolic pathway. Finally, the toxicity of the metabolites was predicted by the Estimation Programs Interface Suite software based on quantitative structure-activity relationships. Decreased toxicity was expected for the most metabolites of the studied NSAIDs except flurbiprofen, whose main metabolite exhibited slightly more toxicity. The present study provided a preliminary foundation to understand the metabolites of some NSAIDs and their toxicity, which was of great significance in animal food safety.