毛细管电泳拆分手性药物速差模式的开发

发布时间：2018-05-23 20:56

本文选题：毛细管电泳 + 速差　；参考：《天津大学》2014年硕士论文

【摘要】：毛细管电泳法是手性药物分离常用方法之一，，一般在缓冲液中直接加入手性选择剂，根据其与药物手性异构体的作用不同而实现手性分离，而研发高效的手性选择剂是传统毛细管电泳技术的关键。为了突破手性选择剂的限制，我们开发了毛细管电泳速差(Velocity gap, VG)模式。这种新方法利用两个连续的电场强度使样品在毛细管中的运动过程分为第一运动相和第二运动相，通过调节第二运动相与第一运动相电场强度的比值，使手性药物两对映体间的速度差异增大。通过这种方法，手性分离的分辨率显著提高。本实验首先以特布他林为样品，在毛细管电泳上成功实现了速差效应对分离度的增加。为了证明速差模式的普适性，接着对特布他林、扑尔敏、盐酸异丙嗪进行了毛细管电泳条件的优化，通过对硫酸特布他林、扑尔敏、盐酸异丙嗪这三种外消旋体药物的速差手性分离验证了新方法的可行性。在相同的条件下（背景缓冲液、手性选择剂、有效分离长度等），样品在传统毛细管区带电泳模式下分离只能被部分分离，而在毛细管电泳速差模式下分离度大大提高，其中特布他林由1.39提高到5.26，扑尔敏由1.24提高到4.12，盐酸异丙嗪由1.21提高到4.79，且分离度还可进一步提高。实验中还对速差模式分离出的两峰纯度进行了初步验证，图谱显示速差模式分离开的两对映体峰基本无杂质存在。所有结果显示，速查模式能够提高毛细管区带电泳的分离能力，即使利用拆分能力较弱的手性选择剂也可得到很好的手性分离效果。
[Abstract]:Capillary electrophoresis is one of the commonly used methods for the separation of chiral drugs. Generally, chiral selectors are added directly to the buffer solution, and the chiral separation is realized according to their different action with the chiral isomers of the drugs. The development of high efficient chiral selectors is the key of traditional capillary electrophoresis. In order to overcome the limitation of chiral selector, we developed a capillary electrophoresis velocity-velocity app (VGG) model. The new method uses two successive electric field intensities to divide the moving process of the sample into the first moving phase and the second moving phase, by adjusting the ratio of the electric field intensity of the second moving phase to the first moving phase. The velocity difference between the two enantiomers of chiral drugs is increased. By this method, the resolution of chiral separation is improved significantly. In this experiment, terbutaline was used as the sample, and the separation degree was increased by the klystron effect on capillary electrophoresis. In order to prove the universality of the klystron mode, the capillary electrophoresis conditions of terbutaline, chlorpheniramine and promethazine hydrochloride were optimized. The chiral separation of promethazine hydrochloride, three racemic drugs, proved the feasibility of the new method. Under the same conditions (background buffer, chiral selector, effective separation length, etc.), the separation of the sample can only be partially separated in the traditional capillary zone electrophoresis mode, but the separation degree is greatly improved in the capillary electrophoresis klystron mode. Terbutaline increased from 1.39 to 5.26, chlorpheniramine from 1.24 to 4.12, promethazine hydrochloride from 1.21 to 4.79, and the degree of separation could be further improved. In the experiment, the purity of two peaks separated by klystron mode was preliminarily verified, and the spectra showed that there were almost no impurities in the two enantiomers separated by klystron mode. All the results show that the rapid detection mode can improve the separation ability of capillary zone electrophoresis, even by using the chiral selector with weak resolution ability, a good chiral separation effect can be obtained.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：O658.9;R917

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