| Bioactivity of chiral drugs is closely related to the stereo structures. Nowadays the development and production of optically pure drugs is the trend of new drugs research, therefore the study on chiral drugs analysis has become more and more importance, and has become a hot and difficult topic in analysis science. Capillary electrophoresis (CE) has manifested its versatility and potential in the separation of chiral drugs, and become one of the most commonly used separation technique, because of its high efficiency, rapid analysis, wide range of separation modes and low consumption of buffer and samples etc. In CE chiral separation, the chiral selector is usually dissolved in the running buffer to provide chiral environment. So the two enantiomers can be separated owing to the difference of the interactions between chiral selectors and enantiomers and thus the difference of electrophoretic mobilities.In this dissertation, several chiral compounds were separated with cyclodextrins and macrocyclic antibiotic as chiral selector respectively, the theory and method of chiral separation was investigated forwardly, and some original studies was carried out:(1) Developed methods for enantioseparation of some axis asymmetry compounds allenic acids.(2) Developed a new method for separation and sensitive determination of rivastigmine enantiomers.(3) Developed a sensitive and high efficiency method for chiral separation of anionic compounds in a short analysis time.(4) Developed a high efficiency and fast method for separation of folinic acid diastereomeric. (5) Developed a method for separation of several anionic compounds in low concentration, with large-volume sample stacking and anion-selective exhaustive injection technique.(6) Developed some methods for separation several new chiral compounds.This dissertation consists of seven chapters.Chapter 1: In this chapter, the theoretical, methodological, and the achievements of chiral separation are reviewed from the chiral selector type.Chapter 2: Enantioseparation of chiral aryl allenic acids by micellar electrokinetic chromatography (MEKC) with cyclodextrins (CDs) as chiral selectors was described. In order to optimize the operational parameters, the effect of the type of CDs and concentration, sodium dodecyl sulfate (SDS), and organic modifier, as well as the buffer ionic strength and pH on enantioseparation were studied. Under the optimal conditions, baseline separations of all seven allenic acid enantiomers were achieved. Furthermore, the result of method validation in terms of repeatability, linearity, limit of detection (LOD), and limit of quantitation (LOQ) were satisfied. Using the present method, the optical purity of a nonracemic sample with the enantiomeric excess (ee%) value of 99.65% was determined.Chapter 3: A sensitive method for enantioseparation of a basic drug rivastigmine and determination of its optical impurity by capillary electrophoresis with highly sulfatedβ-cyclodextrin (HS-P-CD) as the chiral selector was described in weak acid conditions. In order to suppress the adsorption of rivastigmine on the capillary wall due to the electrostatic interaction, dynamically coated capillary with the linear polyacrylamide was used. The neutral polymer coating suppressed the EOF successfully, and the separation efficiency was improved. Under the optimal condition, rivastigmine was baseline separated, and the detection sensitivity was improved with 1.6 times. The optical purity of nonracemic rivastigmine with the enantiomeric excess (ee) value of 99.14% was determined. Chapter 4: An approach for improving the separation performance of the enantioseparation by CE with vancomycin as chiral selector is described. In the present method, a solution of poly(dimethylacrylamide) (PDMA) was used for dynamic coating of the capillary wall to minimize the adsorption of vancomycin onto the capillaiy wall, and to depress the EOF. It was found that the resulting coating can withstand hundreds runs without losing its function. Moreover, a partial filling technique was applied to avoid interference in detection caused by the presence of vancomycin in the buffer. Under the optimal conditions, all tested enantiomers, including FMOC amino acids derivatives, ketoprofen and fenoprofen, were baseline-separated in less than 4.2 min.Chapter 5: An improved method for separation and determination of the optical purity of folinic acid diastereomeric is described by capillary electrophoresis with vancomycin as chiral selector in PDMA dynamically coated capillary. In order to improve separation factors and efficiency, effects of the concentration of organic modifier and vancomycin, the buffer pH and ionic strength, and the separation voltage and column temperature on the separation were investigated and the optimal conditions were established as follows: 100 mM Tris-Phosphate buffer (pH 6.0) containing 1.0 mM vancomycin and 5% acetonitrile at 30℃with 15 kV applied voltage on PDMA dynamically coated capillary. Under the optimal method, the folinic acid diastereomeric was baseline separated, and (6S,2S')-calcium folinate sample with optical impurity at the level of 0.08% was determined with high-low injection technique. Separation time is 7.5 min.Chapter 6: A method for separation of low concentration of chiral compounds was described based on the chapter 4, using large-volume sample injection stacking and anion-selective exhaustive injection technique. In this experiment, the effects of volume of injection with hydrodynamic, electrokinetic injection time, and the sample concentration on the resolution, enhancement factor of detection sensitivity and others was investigated. With this injection technique, the limit detection of the single enantiomer was 3.75×10-7 g/L (375 ppt), and the detection sensitivity was improvedwith 1.1×10 5 fold. Finally, the method was used in separation of low concentration ofFMOC-amino acids, the result was satisfied.Chapter 7: Developed some methods for separation of several new chiral compounds by capillary electrophoresis.
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