Liu Ke, Zhong Dafang, Chen Xiaoyan
Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, PR China.
Bioanalysis. 2009 Jun;1(3):561-76. doi: 10.4155/bio.09.31.
Today, approximately 60% of synthetic drugs are chiral and 88% of these chiral synthetic drugs are used therapeutically as racemates. However, for many racemic drugs, their stereospecific plasma pharmacokinetics in humans are not known due to the limitations of the analytical methods. Nowadays, liquid chromatography (LC)-tandem mass spectrometry (MS/MS) methods based on various chiral stationary phases (CSPs), with a high degree of specificity and sensitivity, have been widely used in enantioselective determination of chiral drugs and/or their metabolites in human plasma. The technologies and issues when coupling chiral chromatography with MS/MS detection in bioanalytical methods will be reviewed herein. The introduction and applications of various CPSs, including polysaccharide-, macrocyclic glycopeptide-, protein- and cyclodextrin-based phases, are described here. This review also includes a discussion of interface and matrix effects in enantioselective LC-MS/MS methods.
如今，约60%的合成药物是手性的，其中88%的手性合成药物以消旋体形式用于治疗。然而，对于许多外消旋药物，由于分析方法的局限性，其在人体中的立体特异性血浆药代动力学尚不清楚。如今，基于各种手性固定相（CSP）的液相色谱（LC）-串联质谱（MS/MS）方法具有高度的特异性和灵敏度，已广泛用于对人血浆中手性药物和/或其代谢物进行对映体选择性测定。本文将综述生物分析方法中手性色谱与MS/MS检测联用的技术及问题。这里描述了各种CSP的介绍和应用，包括基于多糖、大环糖肽、蛋白质和环糊精的固定相。本综述还讨论了对映体选择性LC-MS/MS方法中的接口和基质效应。
