Establishment and validation of an In Vitro evaluation system for human liver UDP-glucuronosyltransferase activity and drug inhibition study
10.12360/CPB202401086
- VernacularTitle:人常见肝UGTs活性与抑制体外评价体系的建立与验证
- Author:
Jing ZHANG
1
;
Hang LI
;
Xue-Xia ZHANG
;
Shuai-Bing LIU
Author Information
1. 郑州大学第一附属医院药学部
- Keywords:
UDP-glucuronosyltransferases;
human liver micro-somes;
probe substrate method;
inhibitory effect;
liquid chroma-tography-tandem mass spectrometry;
drug-drug interactions
- From:
Chinese Pharmacological Bulletin
2024;40(10):1990-1996
- CountryChina
- Language:Chinese
-
Abstract:
Aim To establish a reliable in vitro evaluation sys-tem to assess human liver UGTs activities and the inhibitory effect of drugs on human liver UGTs and validate its accuracy and stability.Methods Six probe substrate of the six major subtypes of human liver microsomal UGT enzymes were select-ed.The activity of human liver microsomal UGT enzymes was determined under optimized incubation conditions using a metab-olite generation method.The concentrations of metabolites were determined using a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Known inhibitors were used to verify the established incubation system.Results The estab-lished LC-MS/MS analysis method complied with the require-ments of bioanalysis.In the incubation system of this experi-ment,known UGT inhibitors exhibited significant inhibitory effects.Conclusions This study successfully establishes an ac-curate and reliable in vitro evaluation system,which can be used to assess the in vitro inhibition of drugs on UGT enzymes,provi-ding important guidance for drug development and rational clini-cal medication.
