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手性电动迁移技术分析药物及其代谢物(2010-2020 年)。

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010-2020).

机构信息

Institute for Infectious Diseases, University of Bern, Bern, Switzerland.

出版信息

Electrophoresis. 2021 Sep;42(17-18):1744-1760. doi: 10.1002/elps.202000383. Epub 2021 Feb 19.

Abstract

The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis- based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field-amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.

摘要

在 2010 年至 2020 年期间,毛细管电泳技术在体液、组织和体外制剂中对药物及其代谢物的对映选择性测定的进一步发展和应用继续证明了其在生物分析中的有用性和吸引力。本文讨论了基于毛细管电泳的手性药物生物分析的原理和重要方面,综述了过去 10 年报道的分析方法,并概述了这一时期所取得的主要成就。对于带有电荷手性选择器的系统,特别关注采用场放大样品进样的分析方法,以实现对分析物 ppb 水平的测定,并优化在线孵育程序,以快速评估代谢途径。讨论的应用包括药物对映异构体在体内和体外的药代动力学、抑制剂对代谢步骤的影响、体内和体外药物代谢的立体选择性阐明,以及毒理学、法医学和兴奋剂分析中的药物对映异构体。

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