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Front. Pharmacol. | doi: 10.3389/fphar.2018.00130

Characterization of the in vitro metabolic profile of evodiamine in human liver microsomes and hepatocytes by UHPLC-Q Exactive mass spectrometer

 Qingwang Liu1*, Zhaowei Zhang2, Tianzi Fang2, Hongyun Zhou2 and Jie Yuan3
  • 1Hefei Institute of Technology Innovation, Hefei Institutes of Physical Science (CAS), China
  • 2Department of pharmacy, Jinhua Central Hospital, China
  • 3Anhui Provincial Institutes Food and Drug Control, China

Evodiamine is an indoloquinazoline alkaloid isolated from the fruit of Evodia rutaecarpa, which has a wide range of pharmacological effects like anti-tumor and anti-inflammatory effects. This study was intended to investigate the metabolic characteristics of evodiamine in human liver microsomes and hepatocytes by ultra-high performance liquid chromatography (UHPLC) coupled with a Q Exactive Mass mass Spectrometerspectrometer. A total of twelve phase I metabolites were detected in human liver microsomes; whereas in human hepatocytes a total of nineteen metabolites, including seven phase II metabolites were detected. The structures of the metabolites were characterized based on their accurate masses, fragment ions, and chromatographic retention times. Four metabolites (M1, M2, M5 and M7) were further unambiguously confirmed by matching their retention times, accurate masses and fragment ions with those of their reference standards. Among these metabolites, twelve metabolites are first identified (M2, M5-M8, M10-M13 and M17-M19). The current study revealed that oxygenation, N-demethylation, dehydrogenation, glucuronidation and GSH conjugation were the major phase I metabolic reaction, and glucuronidation and GSH conjugation were the major phase II metabolic pathways for evodiamine. This study elucidated the detailed metabolite profiles of evodiamine, which is helpful in predicting in vivo metabolism of evodiamine in human body and in understanding the elimination mechanism of evodiamine and, in turn, the effectiveness and toxicity.

Keywords: Evodiamine, Metabolite identification, human liver microsomes, Human hepatocytes, LC-MS

Received: 29 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

Judith M. Rollinger, University of Vienna, Austria

Reviewed by:

Xiaoying Zhang, Northwest A&F University, China
Marinella De Leo, Dipartimento di Farmacia, Università degli Studi di Pisa, Italy
Marc Poirot, Institut National de la Santé et de la Recherche Médicale (INSERM), France  

Copyright: © 2018 Liu, Zhang, Fang, Zhou and Yuan. 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 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: Dr. Qingwang Liu, Hefei Institute of Technology Innovation, Hefei Institutes of Physical Science (CAS), Hefei, China, liuqingwang312@163.com