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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01266

Pharmacokinetics and metabolite profiling of trepibutone in rats using ultra high performance liquid chromatography combined with hybrid quadrupole-orbitrap and triple quadrupole mass spectrometers

 Zhi Sun1, Jie Yang1,  Liwei Liu1,  Yanyan Xu1, lin Zhou1, Qingquan Jia2,  Yingying Shi1, Xiangyu Du3, Jian Kang1* and  Lihua Zuo1*
  • 1Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, China
  • 2Shenyang Pharmaceutical University, China
  • 3School of Basic Medical Sciences, Henan University, China

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. Totally, thirty metabolites were identified in plasma and urine in total by Q-Exactive high resolution mass spectrometry, and several common metabolic pathways were observed such as dealkylation, oxidation, reduction, glucuronidation and so on. The research provides more information of trepibutone in pharmacodynamics and toxicology and will assist the usage in clinic.

Keywords: Trepibutone, pharmacokinetics, metabolite profiling, UHPLC-MS/MS, UHPLC-Q-Orbitrap HRMS

Received: 07 Mar 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Sun, Yang, Liu, Xu, Zhou, Jia, Shi, Du, Kang and Zuo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mr. Jian Kang, Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China, kangjian_yxb@163.com
Dr. Lihua Zuo, Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China, zuolihua2013@126.com