本文選題：毛細(xì)管電泳 + 速差��； 參考：《天津大學(xué)》2014年碩士論文

【摘要】：毛細(xì)管電泳法是手性藥物分離常用方法之一，，一般在緩沖液中直接加入手性選擇劑，根據(jù)其與藥物手性異構(gòu)體的作用不同而實現(xiàn)手性分離，而研發(fā)高效的手性選擇劑是傳統(tǒng)毛細(xì)管電泳技術(shù)的關(guān)鍵。為了突破手性選擇劑的限制，我們開發(fā)了毛細(xì)管電泳速差(Velocity gap, VG)模式。這種新方法利用兩個連續(xù)的電場強(qiáng)度使樣品在毛細(xì)管中的運(yùn)動過程分為第一運(yùn)動相和第二運(yùn)動相，通過調(diào)節(jié)第二運(yùn)動相與第一運(yùn)動相電場強(qiáng)度的比值，使手性藥物兩對映體間的速度差異增大。通過這種方法，手性分離的分辨率顯著提高。本實驗首先以特布他林為樣品，在毛細(xì)管電泳上成功實現(xiàn)了速差效應(yīng)對分離度的增加。為了證明速差模式的普適性，接著對特布他林、撲爾敏、鹽酸異丙嗪進(jìn)行了毛細(xì)管電泳條件的優(yōu)化，通過對硫酸特布他林、撲爾敏、鹽酸異丙嗪這三種外消旋體藥物的速差手性分離驗證了新方法的可行性。在相同的條件下（背景緩沖液、手性選擇劑、有效分離長度等），樣品在傳統(tǒng)毛細(xì)管區(qū)帶電泳模式下分離只能被部分分離，而在毛細(xì)管電泳速差模式下分離度大大提高，其中特布他林由1.39提高到5.26，撲爾敏由1.24提高到4.12，鹽酸異丙嗪由1.21提高到4.79，且分離度還可進(jìn)一步提高。實驗中還對速差模式分離出的兩峰純度進(jìn)行了初步驗證，圖譜顯示速差模式分離開的兩對映體峰基本無雜質(zhì)存在。所有結(jié)果顯示，速查模式能夠提高毛細(xì)管區(qū)帶電泳的分離能力，即使利用拆分能力較弱的手性選擇劑也可得到很好的手性分離效果。
[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.
【學(xué)位授予單位】：天津大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：O658.9;R917

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