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毛细管电泳对映体特异性分析:在药物代谢和药代动力学中的应用

Enantiospecific analysis by capillary electrophoresis: applications in drug metabolism and pharmacokinetics.

作者信息

Hadley M R, Camilleri P, Hutt A J

机构信息

Department of Analytical Sciences, SmithKline Beecham Pharmaceuticals, Tonbridge, Kent, UK.

出版信息

Electrophoresis. 2000 Jun;21(10):1953-76. doi: 10.1002/1522-2683(20000601)21:10<1953::AID-ELPS1953>3.0.CO;2-G.

Abstract

Enantiospecific analysis has an important role in drug metabolism and pharmacokinetic investigations and its now no longer acceptable to determine total drug, or metabolite, concentrations following the administration of a racemate. Inspite of the fact that capillary electrophoresis (CE) has become an essential technique in pharmaceutical and enantiospecific analysis, the chromatographic methodologies remain the most commonly used approach for the determination of the enantiomeric composition of drugs in biological fluids. The application of CE to bioanalysis has been slow, which is in part associated with the complexity of biological matrices together with the relatively poor concentration limits of detection achievable. However, as a result of its versatility, high separation efficiency, minimal sample requirements, speed of analysis and low consumable expense CE is likely to play an increasingly significant role in the area. This review present an overview of enantiospecific CE in bioanalysis in which the approaches to enantiomeric resolution and the problems associated with biological matrices are briefly discussed. The application of enantiospecific CE to samples of biological origin is illustrated using examples where the methodology has either solved an analytical problem, or provided a useful alternative to the currently available chromatographic methods. Such improvements in methodology are associated with either the high separation efficiency and/or microanalytical capabilities of the technique. Enantiospecific CE will not replace the chromatographic methodologies but does provide the bioanalyst with a useful addition to his armamentarium.

摘要

对映体特异性分析在药物代谢和药代动力学研究中具有重要作用,在给予外消旋体后测定药物或代谢物的总浓度已不再被接受。尽管毛细管电泳(CE)已成为药物和对映体特异性分析中的一项重要技术,但色谱方法仍然是测定生物流体中药物对映体组成最常用的方法。CE在生物分析中的应用进展缓慢,部分原因是生物基质的复杂性以及可实现的相对较差的检测浓度限。然而,由于其通用性、高分离效率、对样品要求极低、分析速度快和耗材成本低,CE在该领域可能会发挥越来越重要的作用。本综述概述了对映体特异性CE在生物分析中的应用,其中简要讨论了对映体拆分方法以及与生物基质相关的问题。通过一些示例说明了对映体特异性CE在生物源样品中的应用,这些示例中该方法要么解决了分析问题,要么为目前可用的色谱方法提供了有用的替代方法。方法学上的这些改进与该技术的高分离效率和/或微量分析能力有关。对映体特异性CE不会取代色谱方法,但确实为生物分析人员提供了一种有用的补充手段。

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