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手性毛细管电泳技术拆分β受体阻滞剂的进展。

Advances in the enantioseparation of β-blocker drugs by capillary electromigration techniques.

机构信息

Istituto di Metodologie Chimiche, Consiglio Nazionale delle Ricerche, Area della Ricerca di Roma, Monterotondo Scalo, Rome, Italy.

出版信息

Electrophoresis. 2011 Oct;32(19):2602-28. doi: 10.1002/elps.201100153. Epub 2011 Sep 8.

Abstract

β-Blocker drugs or β-adrenergic blocking agents are an important class of drugs, prescribed with great frequency. They are used for various diseases, particularly for the treatment of cardiac arrhythmias, cardioprotection after myocardial infarction (heart attack), and hypertension. Almost all β-blocker drugs possess one or more stereogenic centers; however; only some of them are administered as single enantiomers. Since both enantiomers can differ in their pharmacological and toxicological properties, enantioselective analytical methods are required not only for pharmacodynamic and pharmacokinetic studies but also for quality control of pharmaceutical preparations with the determination of enantiomeric purity. In addition to the chromatographic tools, in recent years, capillary electromigration techniques (CE, CEC, and MEKC) have been widely used for enantioselective purposes employing a variety of chiral selectors, e.g. CDs, polysaccharides, macrocyclic antibiotics, proteins, chiral ion-paring agents, etc. The high separation efficiency, rapid analysi,s and low consumption of reagents of electromigration methods make them a very attractive alternative to the conventional chromatographic methods. In this review, the development and applications of electrodriven methods for the enantioseparation of β-blocker drugs are reported. The papers concerning this topic, published from January 2000 until December 2010, are summarised here. Particular attention is given to the coupling of chiral CE and CEC methods to MS, as this detector provides high sensitivity and selectivity.

摘要

β-受体阻滞剂或β-肾上腺素能阻滞剂是一类重要的药物,使用频率很高。它们用于治疗各种疾病,特别是心律失常、心肌梗死后的心脏保护(心脏病发作)和高血压。几乎所有的β受体阻滞剂都具有一个或多个手性中心;然而,只有其中一些被用作单一对映体。由于两种对映体在药理学和毒理学性质上可能有所不同,因此需要对映体选择性分析方法,不仅用于药效学和药代动力学研究,还用于药物制剂的质量控制,以确定对映体纯度。除了色谱工具外,近年来,毛细管电泳迁移技术(CE、CEC 和 MEKC)已广泛用于对映体选择性目的,使用各种手性选择剂,例如 CD、多糖、大环抗生素、蛋白质、手性离子对试剂等。电泳方法的高分离效率、快速分析和试剂消耗低使其成为传统色谱方法的极具吸引力的替代方法。本综述报道了用于分离β受体阻滞剂药物对映体的电驱动方法的发展和应用。总结了 2000 年 1 月至 2010 年 12 月期间发表的有关该主题的论文。特别关注将手性 CE 和 CEC 方法与 MS 耦合,因为该检测器提供高灵敏度和选择性。

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