【作者】 李文婧；

【导师】 包建民；

【作者基本信息】 天津大学 ， 药物分析， 2009， 硕士

【摘要】 近年来,对映异构体的分离成为药物分析中非常重要的研究领域。毛细管电泳在电渗流驱动下形成塞流,试剂、样品消耗少。在毛细管电泳中进行手性分离可以采取在毛细管电泳的背景缓冲液中添加具有手性识别能力的选择剂,或者将手性固定相键合在毛细管内壁,此时毛细管电泳分别采取区带电泳和电色谱的形式。电色谱兼具毛细管电迁移的高效和色谱的选择性,成为近年来对映体分离的热点。环糊精及其衍生物是最为常用的一类手性选择剂,其中磺酸化环糊精应用和研究最为广泛,它具有水溶性好,手性识别能力强,可分离的手性化合物范围广等优点。但是,磺酸化环糊精作为选择剂使用时,要求它结构均一,纯度高,所以反应步骤繁琐,售价非常昂贵。为了解决定位反应的磺酸化环糊精以上不足,本文在大量研究的基础上,设计了含有硅氧键的磺酸化β—环糊精这一分子结构,从统计学和高分子的角度,获得了在电泳中均一化的环糊精。并可以通过硅氧键与毛细管壁键合。所得到产品同样可以获得较好的水溶性。通过对比产品作为手性添加剂和手性固定相在不同pH条件下对电渗流的抑制作用,考察了其电泳行为。在电色谱形式下对电渗流的抑制作用非常明显；作为添加剂时在整个考察pH区间内,电渗流变化平缓。在不同pH值条件下考察pH环境分别对几种代表性手性药物的分离作用,结果显示有的获得了手性分离效果,有的两种对映体在出峰时间上有明显区别。对比其不同作用方式的作用结果,分别对不同药物具有手性分离能力,说明其在不同电泳模式下的作用能力、结合方式有很大差别。利用实验室己建立的电喷雾制备纳米硅球技术,制备带有手性分离基团的纳米级微球。并将其作为手性添加剂考察对电渗流的抑制作用。对手性药物进行分离的过程中对所有的酸性药物无法分离。而对华法令的分离有拖尾现象,说明微球上确实键合上对手性药物具有分离能力的官能团,但其作用能力还非常有限。因此,在制球过程中如何提高硅烷偶联剂与产品的结合能力是制备中的关键技术。更多还原

【Abstract】 In recent years, the separation of enantiomers is of primary importance in pharmaceutical analysis. The main advantage of electromigration techniques is the high efficiency due to the plug-like flow profile caused by the EOF. Furthermore, there is a low solvent and selector consumption. Chiral CE separations of drugs have two major modes:chiral selector is added in buffer as chiral additive, or chiral selector is reacted with the inner surface of capillary as chiral staionary phase. These two modes are called capillary zone electrophoresis and capillary electrochromatography, respectively. The use of cyclodextrins (CDs) for different host-guest complex of enantiomeric pairs of compounds is by far the most common strategy employed for chiral separation by capillary electrophoresis.To solve the problems said above, in this paper, a simpler reaction steps, a cheaper, and a more soluble derivatives ofβ-cyclodextrin (β-CD) was synthesized. This compound also had Si-O bond, which can be reacted with the innfer surface of capillary easily. The substituted degree of this novel chiral selector, sulfated copolymer of acrylamide-β-Cyclodextrin (SPA-β-CD) is homogenous in statistics. In other words, although the substituted degree of every CD in a polymer chain is different, there are no obvious differences of the degree among polymer chains. The product was added into buffer as chiral additive and reacted with the inner surface of capillary respectively. These two modes have very different effect on EOF. For chiral separation, several chiral drugs were separated under different pH value in these two modes. The result shows, both modes have achieved chiral separation, but separation efficiencies of different drugs in the same mode are different. Also, the efficiencies of the same drugs with different mode are different.Furthermore, with the combination of sigle-step electrospray method and sol-gel reaction, nanoparticles bonded with SPA-β-CD were prepared. It was added in buffer. And the result shows, it depressed the EOF of the system. Besides, warfarin was separated with tailing area. So, the ability of these nanoparticles in chiral separation is still to be improved. Thus, it is important to improve the reaction degree of silicane coupling agent and SPA-β-CD更多还原