Application of Ultra High-performance Liquid Chromatography Tandem Mass Spectrometry to Investigate the Regioselective Glucuronidation of Icaritin in Vitro

Yi Rong, Zhiyun Meng, Jian Li, Xiaoxia Zhu, Hui Gan, Ruolan Gu, Zhuona Wu, Wenzhong Sun, Taoyun Liu, Ying Zheng, Mingji Jin, Jian Peng, Xinyu Wang, Guifang Dou

Research output: Contribution to journalArticlepeer-review

Abstract

Icaritin is one of the Epimedium products with various biological activities. In the present study, we developed a rapid, reliable and robust UHPLC-MS/MS method to simultaneously determine unconjugated icaritin and its multiple glucuronides (icaritin-3-glucuronide, icaritin-7-glucuronide and icaritin-3,7-diglucuronide) in microsomal incubation systems, and applied it to study icaritin regioselective glucuronidation in vitro. We identified the involvement of human UDP-glucuronosyltransferase (UGT) isoforms in icaritin metabolism and further studied the kinetic profiles of icaritin glucuronidation using pooled human liver microsomes (HLMs), pooled rat liver microsomes (RLMs), pooled human intestine microsomes (HIMs) and UGTs, respectively. We also evaluated regioselective glucuronidation of icaritin by UGT isoforms and conducted time-dependent experiment to elucidate the metabolic pathways for icaritin clearance. Catalytic efficiency of microsomes is determined according to rank orders of total intrinsic clearance (CL

Original languageAmerican English
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume154
StatePublished - Feb 13 2018

Keywords

  • Enzyme kinetics
  • Glucuronidation/Diglucuronidation
  • Regioselectivity
  • UDP-glucuronosyltransferase/UGT

Disciplines

  • Medicine and Health Sciences

Cite this