【作者】 杜红英；

【导师】 侯经国； 高锦章；

【作者基本信息】 西北师范大学 ， 分析化学， 2005， 硕士

【摘要】 近年来,手性药物的分离在医学界引起了越来越大的兴趣。这是因为手性药物对映体之间药理学性质存在着很大的差异,通常一种异构体有药效,而它的镜像分子药效却很小,甚至完全没有药效或者具有完全相反的药效。为了能准确地了解药效和安全用药,发展和建立简单快速的手性药物对映体的分离分析方法,并用于临床研究和医药质量控制,显得日益迫切。因而对映体的拆分在药物分析、临床科学、生命分离科学中具有十分重要的意义。 毛细管电泳(CE)是分离科学中一种非常有效的手性药物分离技术。由于它具有高效、快速、样品消耗量少、操作简便以及可供选择的分离模式多且变换简单,手性选择试剂直接加入载体电解质中,容易通过选用不同的手性选择试剂和改变背景电解质溶液的组成提高分离选择性等优点而被广泛应用于色谱分离领域。毛细管区带电泳(CZE)是毛细管电泳手性拆分模式中最简单、最常用的分离方法。它通常是在背景电解质溶液中添加各种手性选择剂,构建手性环境,使得对映体与手性添加剂发生相互作用,最终达到分离的目的。 本论文共计五章内容。 第一章:对毛细管区带电泳手性分离方面的研究应用进行了综述。重点介绍了毛细管区带电泳中以环糊精及其衍生物和大环抗生素为手性选择剂的研究进展情况以及毛细管电泳手性分离过程中的动力学和热力学参数的研究。 第二章:以2,6-0-二甲基-β-环糊精(DM-β-CD)为手性选择剂对丙吡胺对映体进行了手性拆分。研究了环糊精类型和浓度对分离的影响,同时考察了背景电解质溶液的pH值,电压以及温度对手性拆分的影响。结果表明,在固定背景缓冲溶液为30mmol/L磷酸氢二钠的条件下,拆分丙吡胺对映体的最佳条件为:25mmol/LDM-β-CD,pH3.50,分离电压14kV,温度23℃。采用DM-β-CD作为手性添加剂可以使丙吡胺对映异构体达到基线分离,为此类药物提供了一种简便、快速、新的毛细管电泳手性分离分析方法。 第三章:运用羟乙基-β-环糊精(HE-β-CD)为手性选择剂,利用毛细管电泳对几种药物对映体进行了拆分研究。考察了HE-β-CD浓度,背景电解质溶液的pH,更多还原

【Abstract】 In recent years, there has been a marked increase in the pharmacological interest of chiral drugs. A pair of ennantiomers of chiral drug gerenally differs in their pharmacological properties as a consequence of steroselective interaction with biological macromalecules such as protein and polysaccharide. Metabolic and regulatory processes mediated by biological systems are sensitive to stereochemistry. In many cases, only is one of a pair of enantiomers responsible for the varied activity while another isomer may exhibit no therapeutic value and even cause many potentially unexpected adverse effects. Therefore, stereochemistry has to be considered when studying xenobiotics, such as drugs, agrochemicals, food additives, flavours or fragrances. Separation and analysis of enantiomers are necessary to obtain optical pure drug for pharamaceutical clinical study, control the enantiomeric purity of products and conduct pharmacokinetic, pharmacodynamic studies and clinical research, etc. Nowadays the separation and analysis of chiral compounds, especially for the chiral drugs, have significance, and have already become one of projects extensively researched in the field of separation science. So, the urgent demand for analytical methods with highly resolution power and high efficiency is recently increasing.Capillary electrophoresis （CE） has emerged as a versatile method for chiral drugs analysis; due to high separation efficiency, excellent compatibility with biological samples, short analysis time, simplicity and low cost. In addition, diverse separation modes and larger numbers of available chiral selectors make CE technique to turn into a very important tool for chiral analysis in the pharmaceutical field. Enantiomers may be recognized stereoselectively only on the stage of their interaction with a chiral selector. Compared to other chromatographic techniques, the combination of chiral electors is much easier in CE technique. Capillary Zone Electrophoresis （CZE） is one of the most simple and effective methods among all of CE operation modes, which is accomplished by adding a chiral selector into the background electrolyte.The dissertation consists of five parts.Chapter 1 reviewed the developments in enantioseparations of chiral compounds using capillary electromigration techniques, especially focused on the state of arts of chiral separation using ctyclodextrins and their derivatives and macrocyclic antibiotics as chiral selectors. In this chapter, the recent development of synergistic effect in capillary electrophoresis enantioseparation is also covered.In Chapter 2, disopyramide racemate was separated with capillary zoneelectrophoresis using 2,6-0-dimethyl -P-cyclodextrin （DM-p-CD） as a chiral selector. Effects of the concentration of DM-P-CD, the pH of background electrolyte, the voltage and the temperature on the enantiomeric separation were investigated. The results showed that the enantioseparation of disopyramide, fixing the concentration of NaH₂PO₄ at 30 mmol/L, were optimized. The optimum operation parameters obtained for the enantioseparation of disopyramide showed as followings: the buffer solution consisted of 25 mmol/L DM-β-CD in NaH₂PO₄ aqueous solution of 30 mmol/L at pH=3.50, the separation voltage set up at 14kV, and the temperature was at 23 ℃.In Chapter 3, four chiral drugs were separated with capillary zone electrophoresis using HE-p-Cyclodextrin （HE-P-CD） as a chiral selector to add into background electolyte. Effects of the concentration of HE-β-CD, the concentration of surfactant, the pH of background electrolyte, the voltage and the temperature on the enantiomeric separation were investigated. The results showed that the enantioseparation conditions of chiral drugs, when fixing the concentration of NaH₂PO₄ at 40 mmol/L, were optimized as followings: the buffer solution consisted of 40 mmol/L NaH₂PO₄ in water containing 25mmol/L HE-P-CD at pH 2.50, the separation voltage applied was at 14 kV, and the temperature at 23℃.In Chapter 4, the enantioseparation of homatropine we更多还原