Faber Helene, Vogel Martin, Karst Uwe
Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstr. 30, Münster 48149, Germany.
Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstr. 30, Münster 48149, Germany.
Anal Chim Acta. 2014 Jun 27;834:9-21. doi: 10.1016/j.aca.2014.05.017. Epub 2014 May 17.
The combination of electrochemistry (EC) and mass spectrometry (MS) has become a more and more frequently used approach in metabolism studies in the last decade. This review provides insight into the importance of metabolism studies during the drug development process and gives a short overview about the conventionally used methods since electrochemistry is often intended to substitute or minimize animal-based studies. The optimization of the electrochemical conditions is of great importance for a successful comparison with in vitro approaches. The type of metabolism reactions, which can be simulated by EC, has been extended with new cell types and working electrodes. Although the mechanism differs from the enzyme-catalyzed turnover, electrochemistry can be used to simulate a significant number of the respective reactions. An expanded set-up consisting of EC, a chromatographic separation and MS allows to distinguish between an electrospray ionization (ESI) in-source and an electrochemical oxidation and provides information on the polarity of the electrogenerated compounds. A main advantage of EC for metabolite generation is the possibility to isolate reactive species because of the purely instrumental approach. Especially when a preparative electrochemical cell with a larger working electrode surface is used, metabolites can be generated in sufficient quantities for their subsequent structure elucidation. Besides, the compounds can also be used for selective trapping experiments with different cell components such as small peptides, proteins or DNA bases. Current and possible future developments and applications of EC are presented and discussed as well.
在过去十年中，电化学（EC）与质谱（MS）相结合已成为代谢研究中越来越常用的方法。本综述深入探讨了药物研发过程中代谢研究的重要性，并简要概述了传统使用的方法，因为电化学常常旨在替代或尽量减少基于动物的研究。优化电化学条件对于与体外方法进行成功比较至关重要。随着新型细胞类型和工作电极的出现，可通过电化学模拟的代谢反应类型得以扩展。尽管其机制与酶催化周转不同，但电化学可用于模拟大量相应反应。由电化学、色谱分离和质谱组成的扩展装置能够区分电喷雾电离（ESI）源内电离和电化学氧化，并提供有关电生成化合物极性的信息。电化学用于生成代谢物的一个主要优点是，由于采用纯仪器方法，有可能分离活性物种。特别是当使用具有较大工作电极表面的制备型电化学池时，能够生成足够量的代谢物以用于后续的结构解析。此外，这些化合物还可用于与不同细胞成分（如小肽、蛋白质或DNA碱基）的选择性捕获实验。本文还介绍并讨论了电化学当前以及未来可能的发展和应用。
