基于手性离子液体的多模式高效毛细管电泳手性药物分析方法研究

The chiral drug analysis is a hot point and difficult topic in the pharmaceutical analysis. The traditional chiral drug analysis often exists in the separation some problems such as high cost and use of large quantity of organic solvents. In this project, two different types of the chiral ionic liquids (CILs), synthesized by ourselves, which are environment friendly, will be linked with high performance capillary electrophoresis (HPCE) which has the characteristics of low consumption and flexible separation modes, will be used as new separation media of HPCE. To explore the separation mechanism and the usage principle of CIL-HPCE methods for the analysis of various chiral drugs such as alkaloids, amino acids etc., and to establish the mathematic formulae for the electrophoretic migration behavior of analytes based on the analysis of the changing regularity of electrophoretic mobilities linked with their structural features. We shall clarify the interaction mechanisms between the chiral ionic liquids used in HPCE separation systems and the analytes. Combined the application rules of the same type of chiral selective reagents used in HPLC and HPCE and the applications in the asymmetric catalysis in organic syntheses of the same type of chiral ionic liquids, we try to reveal their regularities used in chiral drugs analysis. The completion of this project not only can establish the new methods which have the characteristics of green and low consumption, used for separation of chiral drugs in vitro and in vivo, and for chiral enantiomers impurities test; can also enrich the HPCE theory system.

手性药物分析一直是药物分析的热点和难点。传统的手性药物分析往往存在分离成本高，有机溶剂用量大等弊端。本课题将环境友好的手性离子液体（CIL）和低消耗且分离模式灵活多样的高效毛细管电泳（HPCE）有机结合，利用自合成的两种不同类型的CIL作为HPCE手性药物分离的介质体系（其中冠醚金属离子液体为课题组首次合成），探讨其在生物碱、氨基酸等不同类型手性药物分离中的应用及分离机制，通过分析不同电泳模式体系中模型化合物淌度的变化规律及其结构特点，建立影响分析物电泳迁移行为的数学模拟公式。结合同类型手性选择性试剂在HPLC及HPCE分离分析方面的应用规律及同类型CIL在不对称催化有机合成方面的文献报道等，阐明CIL在HPCE手性分离体系中的作用原理，揭示其应用于手性药物分析的规律性。此课题的完成不仅可建立绿色、低耗的HPCE手性药物体内外分离分析及手性对映体杂质检测的新方法，也可丰富HPCE理论体系。

手性药物分析一直是药物分析的热点和难点。传统的手性药物分析往往存在分离成本高，有机溶剂用量大等弊端。本课题将环境友好的手性离子液体和低消耗且分离模式灵活多样的高效毛细管电泳有机结合，利用自合成的手性离子液体作为毛细管电泳手性药物分离的介质体系，探讨了其在生物碱、氨基酸等不同类型手性药物分离中的应用及分离机制，通过分析不同电泳模式体系中模型化合物淌度的变化规律及其结构特点，初步阐明了手性离子液体在毛细管电泳手性分离体系中的作用原理，揭示了其应用于手性药物分析的规律性，丰富了毛细管电泳理论体系；与此同时，课题组建立了数种手性药物分离的新方法，并相继发表在EI，SCI等国际期刊上。