The Study And Application Of Cyclodextrin In Capillary Electrophoresis Of Chiral Separation Of Drugs

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 important,and has been a hot and difficult topic in analytical science.Capillary electrophoresis(CE) has manifested its versatility and potential in the separation of chiral drugs,and become one of the most universally used separation techniques, because of its high efficiency,rapid analysis,wide range of separation modes and low consumption of buffer and sample solutions.CDs and their various derivatives has become the most commonly and effective chiral selector in enantioseparation by capillary electrophoresis owing to their plenty of kinds,the low prices and the excellent chiral recognition capacity.In the second part of this dissertation,two chiral drugs were separated with CDs as chiral selector respectively,the theory and method of chiral separation were also investigated,and some original studies were carried out:1.Developed a new method for enantioseparation of folic acid antagonist PPGA.2.Developed the enantioseparation of four palonosetron hydrochloride based on the high concentration ofβ-CD.This dissertation consists of three parts and four chapters.Partâ… ReviewChapter 1:In this chapter,the theoretical,the methodological,and the progress of chiral separation in capillary electrophoresis are carefully reviewed,especially based on the CDs and other chiral selector.Partâ…¡Study and application of CE in the Enantioseparation of chiral drugsChapter 2:Enantioseparation of folic acid antagonist PPGA by capillary zone electrophoresis(CZE) using HP-β-CD as chiral selector was described.Baseline separation of PPGA stereoisomers was achieved using a running buffer composed of 25 mM NaH₂PO₄,10%(v/v) methanol and 30 mM HP-β-CD(pH 4.0),and the applied voltage was 20 kV. Chapter 3:The enantioseparation of four stereoisomers of palonosetron hydrochloride(PALO) by CZE using high concentrationβ-CD as chiral selector was described.For optimization of the method of enantioseparation,several parameters such asβ-CD concentration,separation buffer pH and concentration,the types and concentration of organic modifiers,and the applied voltage were evaluated.The optimum conditions were obtained as follows:30 mM NaH₂PO₄(pH 3.0) containing 150 mMβ-CD and 10%(v/v) methanol with an applied voltage of 15 kV.Under these conditions,baseline separation of the four PALO stereoisomers was achieved within 35 min,and the reproducibility(expressed as relative standard deviation,RSD) of the migration times and the peak areas were below 0.5%,2.5%(intra-day),and 1.9%, 4.4%(inter-day),respectively.Compared with the results with sodium cholate as chiral selector,there are some obvious differences in the migration times,the peak order and the resolutions of the four PALO enantiomers,which should be due to the different stereo structures of PALO stereoisomers and their different binding capacities withβ-CD and sodium cholate.Partâ…¢Synthesis of preservative 1-MCPChapter 4:A new synthetic route of 1-methylcyclopropene(1-MCP) was designed,and 1-MCP was conveniently included into stable preservative based on CD. The purity and inclusion yield of 1-MCP in the preservative was higher than those from the references and Patents.In addition,the preservative was harmless,and has very high practical value.