RRC ID 56001
Author Todoroki K, Kudoh Y, Nakamura M, Shimizu Y, Sasaki T, Otsuki H, Wada K, Min JZ, Mizuno H, Yoshinari K, Toyo'oka T.
Title Sensitive and Comprehensive LC-MS/MS Analyses of Chiral Pharmaceuticals and Their Hepatic Metabolites Using Ovomucoid Column.
Journal Anal Sci
Abstract A sensitive analytical method was developed for the simultaneous detection of 11 chiral pharmaceuticals and their hepatic metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using an ovomucoid chiral column. After optimization of the LC conditions, all pharmaceuticals examined were enantio-separated with Rs of >0.82 in LC-MS/MS analysis. The limit of detections of all pharmaceuticals by MS/MS detection ranged from 1.2 to 92.3 nM, which is approximately 1000 - 25000 times lower than those obtained by UV detection. From hepatic metabolite analyses in P450-expressing cells, metabolites of three pharmaceuticals were detected and enantio-separated. By using the proposed method, changes in the optical isomer ratio of the hepatic metabolites chlorpheniramine and verapamil caused by differential cytochrome P450 enzyme expression for each isomer, could be successfully traced.
Volume 34(9)
Pages 1011-1015
Published 2018-9-10
DOI 10.2116/analsci.18SCP05
PMID 30033954
MeSH Chromatography, Liquid / methods* Hep G2 Cells Humans Limit of Detection* Liver / metabolism* Pharmaceutical Preparations / chemistry* Pharmaceutical Preparations / metabolism* Stereoisomerism Tandem Mass Spectrometry / methods*
IF 1.618
Times Cited 0
Resource
Human and Animal Cells Hep G2