Pharmacokinetics and Metabolite Profiling of Trepibutone in Rats Using Ultra-High Performance Liquid Chromatography Combined With Hybrid Quadrupole-Orbitrap and Triple Quadrupole Mass Spectrometers

使用超高效液相色谱结合混合四极杆轨道阱和三重四极杆质谱对大鼠曲匹布通的药代动力学和代谢物进行分析

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作者:Zhi Sun, Jie Yang, Liwei Liu, Yanyan Xu, Lin Zhou, Qingquan Jia, Yingying Shi, Xiangyu Du, Jian Kang, Lihua Zuo

Abstract

Trepibutone was widely used for cholelithiasis, cholecystitis, biliary tract dyskinesia, cholecystectomy syndrome, and chronic pancreatitis in clinic. However, few investigations on trepibutone have been conducted. In this study, an accurate, sensitive, and selective analytical method was developed and successfully applied to assess the pharmacokinetic behavior of trepibutone in rats. Trepibutone and carbamazepine (internal standard, IS) were quantified using multiple reaction monitoring (MRM) mode with the transitions of m/z 311.09→265.08 and m/z 237.06→194.08, respectively. The linearity, precision, accuracy, extraction recovery, matrix effect, and stability of the established method were all excellent within acceptable range. A total of 30 metabolites were identified in plasma and urine by Q-Exactive high resolution mass spectrometry, and several common metabolic pathways were observed such as dealkylation, oxidation, reduction, glucuronidation, and so on. This research provides more information on trepibutone in pharmacodynamics and toxicology and will assist the usage of trepibutone in clinical.

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