Ma Liyun, Mao Xiaojing, Sun Xiao, Xu Li
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Pharmacy, Union Hospital of Huazhong University of Science and Technology, Wuhan 430022, China.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Chemosphere. 2017 Nov;186:466-474. doi: 10.1016/j.chemosphere.2017.08.026. Epub 2017 Aug 8.
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.
非甾体抗炎药（NSAIDs）是动物中最常用的药物之一。在本研究中，研究了猪肝微粒体（PLMs）对五种NSAIDs的生物转化。体外实验中，PLMs对所研究的NSAIDs代谢符合伪一级动力学模式。通过高效液相色谱与高分辨率LTQ-Orbitrap质谱联用鉴定代谢产物。证实苯环羟基化是主要代谢途径。最后，基于定量构效关系，使用估算程序接口套件软件预测代谢产物的毒性。除氟比洛芬外，所研究的NSAIDs的大多数代谢产物毒性预计会降低，其主要代谢产物毒性略有增加。本研究为了解某些NSAIDs的代谢产物及其毒性提供了初步基础，对动物食品安全具有重要意义。
