Chiral Separation By Capillary Zone Electrophoresis And A Study On Dynamic And Thermodynamic Parameters In The Enantioseparation Process

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...