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胶束电动毛细管色谱法评价新型手性选择剂克林霉素磷酸对碱性药物的对映体分离能力。

Evaluation of the enantioseparation capability of the novel chiral selector clindamycin phosphate towards basic drugs by micellar electrokinetic chromatography.

机构信息

Department of Analytical Chemistry, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu, China.

出版信息

J Chromatogr A. 2010 Mar 12;1217(11):1806-12. doi: 10.1016/j.chroma.2010.01.043. Epub 2010 Jan 21.

DOI:10.1016/j.chroma.2010.01.043
PMID:20132938
Abstract

To date, a series of chiral selectors have been utilized successfully in capillary electrophoresis (CE). Among these various chiral selectors, macrocyclic antibiotics have been demonstrated to represent powerful enantioselectivity towards many chiral compounds. Differing from macrocyclic antibiotics, the use of lincosamide antibiotics as chiral selectors has not been reported previously. In our recent work, clindamycin phosphate belonging to the group of lincosamides has been first used as a chiral selector in capillary zone electrophoresis (CZE). In this paper, a micellar electrokinetic chromatography (MEKC) method has been developed for the evaluation of enantioseparation capability of this novel chiral selector towards several racemic basic drugs. As observed during the course of this work, clindamycin phosphate allowed excellent separation of the enantiomers of nefopam, citalopram, tryptophan, chlorphenamine, propranolol and metoprolol, as well as partial enantioresolution of tryptophan methyl ester and cetirizine. In this MEKC chiral separation system, different types of anionic surfactants, organic additives and background electrolytes were tested, and satisfactory enantioseparations of basic drugs above-mentioned were achieved using sodium dodecyl sulfate (SDS) as the surfactant, isopropanol as the organic additive, and phosphate as the background electrolyte. Furthermore, both migration times and enantioseparation of the analytes were influenced by several experimental parameters such as pH of the BGE, clindamycin phosphate and SDS concentrations, phosphate and isopropanol concentrations, and applied voltage. Consequently, the effects of these factors on enantioseparations of the studied basic drugs were systematically investigated in order to evaluate the stereoselectivity of clindamycin phosphate in MEKC.

摘要

迄今为止,已有一系列手性选择剂成功应用于毛细管电泳(CE)。在这些不同的手性选择剂中,大环抗生素已被证明对许多手性化合物具有强大的对映选择性。与大环抗生素不同,以前尚未报道过使用林可酰胺类抗生素作为手性选择剂。在我们最近的工作中,克林霉素磷酸酯属于林可酰胺类抗生素,首次被用作毛细管区带电泳(CZE)中的手性选择剂。本文开发了一种胶束电动色谱(MEKC)方法,用于评估该新型手性选择剂对几种外消旋碱性药物的对映体拆分能力。在这项工作的过程中观察到,克林霉素磷酸酯允许纳福泮、西酞普兰、色氨酸、氯苯那敏、普萘洛尔和美托洛尔的对映异构体得到极好的分离,以及色氨酸甲酯和西替利嗪的部分对映体拆分。在该 MEKC 手性分离体系中,测试了不同类型的阴离子表面活性剂、有机添加剂和背景电解质,并使用十二烷基硫酸钠(SDS)作为表面活性剂、异丙醇作为有机添加剂、磷酸盐作为背景电解质,实现了上述碱性药物的满意对映体分离。此外,分析物的迁移时间和对映体分离受到 BGE 的 pH、克林霉素磷酸酯和 SDS 浓度、磷酸盐和异丙醇浓度以及施加电压等几个实验参数的影响。因此,系统研究了这些因素对研究碱性药物对映体分离的影响,以评估克林霉素磷酸酯在 MEKC 中的立体选择性。

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