TY - JOUR
T1 - Application of Ultra High-performance Liquid Chromatography Tandem Mass Spectrometry to Investigate the Regioselective Glucuronidation of Icaritin in Vitro
AU - Rong, Yi
AU - Meng, Zhiyun
AU - Li, Jian
AU - Zhu, Xiaoxia
AU - Gan, Hui
AU - Gu, Ruolan
AU - Wu, Zhuona
AU - Sun, Wenzhong
AU - Liu, Taoyun
AU - Zheng, Ying
AU - Jin, Mingji
AU - Peng, Jian
AU - Wang, Xinyu
AU - Dou, Guifang
PY - 2018/2/13
Y1 - 2018/2/13
N2 - 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
AB - 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
KW - Enzyme kinetics
KW - Glucuronidation/Diglucuronidation
KW - Regioselectivity
KW - UDP-glucuronosyltransferase/UGT
UR - https://digitalcommons.pcom.edu/scholarly_papers/1910
M3 - Article
VL - 154
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -