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评价克拉霉素乳酸盐作为一种新型手性选择剂用于毛细管电泳拆分碱性药物对映体。

Evaluation of clarithromycin lactobionate as a novel chiral selector for enantiomeric separation of basic drugs in capillary electrophoresis.

机构信息

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, P. R. China.

出版信息

Electrophoresis. 2011 Jul;32(14):1898-905. doi: 10.1002/elps.201000630.

Abstract

Nowadays, macrocyclic antibiotics are presenting an increasing number of enantioseparation applications. The macrocyclic antibiotics used as chiral selectors in capillary electrophoresis (CE) include the ansamycins and the glycopeptides. The macrolides, another important class of macrocyclic antibiotics, have been reported as a new type of chiral selectors recently. In this study, clarithromycin lactobionate (CL), belonging to the group of macrolide antibiotics, was first investigated for its potential as a novel chiral selector in CE for enantiomeric separation of several basic drugs. As observed, CL allowed excellent separation of the enantiomers of metoprolol, atenolol, propranolol, bisoprolol, esmolol, ritodrine, and amlodipine, as well as partial enantioresolution of labetalol and nefopam. In addition, CL possesses advantages such as high solubility and low viscosity in the solvent and very weak UV absorption. In the course of this study, it was found that both migration times and enantioseparation of the basic drugs were influenced by several experimental parameters, e.g. selector concentration, the composition and pH of the BGE, the type and concentration of organic modifier, and applied voltage. Thus, the effects of these factors were systematically investigated, and satisfactory enantioseparations of the studied drugs were achieved at the buffer pH range of 7.3-7.5 using 12.5 mM borax buffer with 50% v/v methanol, 60 mM CL, and 20 kV applied voltage. Moreover, comparison of the influences of the studied parameters was further investigated by means of Statistical Product and Service Solutions (SPSS) in this article.

摘要

如今,大环抗生素在对映体分离中的应用越来越多。在毛细管电泳(CE)中用作手性选择剂的大环抗生素包括安莎霉素类和糖肽类。大环内酯类,另一种重要的大环抗生素类,最近也被报道为一种新型手性选择剂。在本研究中,克拉霉素乳糖酸盐(CL),属于大环内酯类抗生素,首次被研究作为 CE 中对映体分离几种碱性药物的新型手性选择剂的潜力。结果表明,CL 允许美托洛尔、阿替洛尔、普萘洛尔、比索洛尔、艾司洛尔、利托君和氨氯地平的对映异构体得到极好的分离,以及拉贝洛尔和奈福泮的部分对映体拆分。此外,CL 具有溶剂中高溶解度和低粘度以及非常弱的紫外吸收等优点。在本研究过程中,发现碱性药物的迁移时间和对映体分离均受几种实验参数的影响,例如选择剂浓度、BGE 的组成和 pH 值、有机改性剂的类型和浓度以及施加的电压。因此,系统地研究了这些因素的影响,并在缓冲液 pH 值为 7.3-7.5 范围内,使用 12.5 mM 硼砂缓冲液(含 50% v/v 甲醇)、60 mM CL 和 20 kV 施加电压,实现了研究药物的满意对映体分离。此外,本文还通过统计产品和服务解决方案(SPSS)进一步研究了研究参数的影响。

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