| Chirality is a natural phenomenon in chemistry, material, environmental, biomedical and pharmaceutical fields. Chiral separation has become a hot topic in analytical chemistry area. Among the modern techniques, high performance capillary electrophoresis (HPCE) is the most attractive analytical tool emerging after liquid chromatographic approaches. Cyclodextrins and their derivatives have been successfully applied as chiral selectors in HPCE. Based on the development of capillary electrophoresis methods for high efficient separation of enantiomers and the exploration of their application, the main investigation and evolution are summarized as follows:In the introductory chapter, the application of the high performance capillary electrophoresis, especially for non-aqueous capillary electrophoresis, in chiral analysis is reviewed. The research proposal of first part of this dissertation was presented.In chapter two, Uniform Design method was employed to investigate the influence of separation conditions. Parameters such as buffer pH and chiral selector HP-P-CD concentration were shown critical to control the chiral separations. Besides, organic modifier also played an important role in optimizing separation. a-Bencynonatine and demethylbencynonatine were successfully resolved by aqueous capillary electrophoresis (ACE) by adding organic solvent to aqueous running solutions and establishing suitable separation conditions. For penequinine, no separation between I and II racemates was found, but chiral separation was obtained for enantiomer I or II.In chapter three, an anionic cyclodextrin, heptakis (2, 3-di-O-methyl-6-O-sulfato)-P-cyclodextrin (HDMS-β-CD) has been selected as chiral selective agent in the running electrolyte for the electrophoretic chiral separation of anticholinergic drugs. The influence of several factors on the chiral separation of drug enantiomers was investigated. The enantiomeric resolution was mainly influenced by CD types, HDMS-β-CD concentration and acidity of background electrolyte. The effects of the length of capillary, applied voltage and sample plug length on the enantiomeric resolution were also discussed. The results showed that fifteen anticholinergic drugs and structrurally similar intermediates, and eight other base pharmaceutical enantiomers were baseline separated by nonaqueous capillary electrophoresis (NACE). The NACE method is simple, rapid, accurate, and has been proved to be a very powerful tool in chiral separations.In chapter four, to investigate the difference of the chiral separation of drug enantiomers in both capillary electrophoresis modes, some assays were developed for chiral drugs in aqueous solution. Compared with them, the advantage of NACE chiral separation was that higher electric field strength could be applied. The NACE method provided greater efficiency, achieving baseline resolution for 23 basic compounds, whereas, ACE method cost longer time and obtained lower resolution degree because of Joule heating brought from higher ionic strength or higher electric field strength. So NACE is a very powerful tool in chiral analysis.In addition, the application of cyclodextrins and their derivatives as chiral selectors in chiral analysis was summarized according to different buffer system and CD types, and the mechanism of chiral separations was discussed. The results showed that the solubility of CDs played a very important role in chiral resolution. Charged CDs might improve the chiral recognition of enantiomeric compounds because electrostatic interaction was proved to be a powerful tool. Comparison of the studied drug structures combined with the chiral separation result, it was found that the chiral separation of enantiomer compounds had evidently relation with their structures. It was shown that the chiral center with two or more ring groups was greatly important for chiral recognition of CDs or resolution of chiral compounds because the bigger chiral inclusion difference could be induced as a result of steric hindrance. In addition to two ring substituent groups, the chiral center with ester bond was more favorable for chiral separation of enantiomers than one with ether bond because of forming hydrogen bond between the hydroxyl groups beside the CDs and ester bond. Besides, heterogeneous atoms at key position might also influence on the resolution.Chapter five describes the application of capillary electrophoresis chiral separation. The above established ACE method was used for separation and determination of the zolmitriptan enantiomers, and for the quality control of the chiral purity. Determination of commercial medicines was performed and shown acceptable. The above NACE method was used for separating and determining the amphetamine tartrate enantiomers, and for choosing the optimum experiment condition of the unsymmetry synthesis. The results showed that the proposed method is simple, rapid, accurate, and applicable.Research and development of antibacterial drugs is a hot topic in the world. Traditional drug screening assay was time-consuming and laborious. To work out somestrategies for screening traditional drug, HPCE technique was employed to study bacteria and its interaction with traditional drugs. The main points are summarized as follows:In chapter six, the application of the high performance capillary electrophoresis in microbe analysis is reviewed. The research proposal of the second part of this dissertation was presented.In chapter seven, based on bacteria carry charged or chargeable groups on their outer surface, bacteria undergo electrophoresis in free solution with their migration depending on the ionic strength and the pH of the buffer solution. Therefore, the experimental conditions of influencing enterotoxigenic coliform (E. coli) analysis were examined, such as different buffer types, growth stages, and bacteria sample storage etc. The electrophoretic behaviour was improved by adding polyethylene oxide (PEO) to the running buffer. Rapid Separation and determination of E. coli by capillary zone electrophoresis (CZE) was developed. Besides, the CZE was applied to distinguish between the intact and damaged (or inactive) bacteria with different surface ionization, and rapid characterization of E. coli was achieved by CZE and the relevant parameters. Based on the extraction and separation of Chinese traditional medicine, rhizoma coptidis, fructus evodiae and their compounds, the interaction between their extract and E. coli was investigated utilizing CZE, respectively. It was found that the CE could be conveniently used for rapid and highly sensitive examination of microbe interaction with drugs. It was proved that these drugs studied might inhibit microbe growth to some degree. This proposed CE method could become an effective tool for screening of Chinese traditional medicine. |
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