Structural elucidation of metabolites of ginkgolic acid in rat liver microsomes by ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry and hydrogen/deuterium exchange.
Ginkgolic acids have been shown to possess allergenic as well as genotoxic and cytotoxic properties. The question arises whether the metabolism of ginkgolic acids in the liver could decrease or increase their toxicity. In this study, the in vitro metabolism of ginkgolic acid (15:1, GA), one component of ginkgo acids, was investigated as a model compound in Sprague-Dawley rat liver microsomes. The metabolites were analyzed by ultra-performance liquid chromatography coupled with photodiode array detector/negative-ion electrospray ionization tandem mass spectrometry (UPLC-PDA/ESI-MS/MS) and hydrogen/deuterium (H/D) exchange. The result showed that the benzene ring remained unchanged and the oxidations occurred at the side alkyl chain in rat liver microsomes. At least eight metabolites were found. Among them, six phase I metabolites were tentatively identified. This study might be useful for the investigation of toxicological mechanism of ginkgolic acids.
Liu
Z H
ZH
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People's Republic of China.
Chen
J
J
Yu
L S
LS
Jiang
H D
HD
Yao
T W
TW
Zeng
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D041961:Deuterium Exchange Measurement / Q000379:methods*; D020441:Ginkgo biloba / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
D012459:Salicylates; C112485:ginkgolic acid