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Study Of Enantiomeric Separation Methods Of Several Chiral Compounds

Posted on:2010-12-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y Q ChenFull Text:PDF
GTID:2234360305485801Subject:Drug Analysis
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Separation of enantiomeric, with increasing importance in pharmaceutical research is now a hot topic modern scientific fields. Two enantiomers of chiral drugs usually possess different pharmacokinetic, pharmacodynamics and pharmacological action. Accordingly, the availability of chiral analytical separation methods are important in studying and understanding the pharmacokinetic processes, the pharmacological and/or toxicological effects and the quality control of many drugs. At present, the methods for chiral separation can be divided into chiral stationary phase and chiral mobile phase. The key of chiral mobile phase addition method is to find a suitable chiral selector. Room Temperature Ionic liquids(RTIL), satls that are liquid at ambient temperature, are normally composed of relatively large organic cations and inorganic or organic anions which are liquids at room temperature. Unlike molecular liquids, ionic liquids, which are polar solvents, are environmentally benign, known as green solvents. According to different needs, we can synthesis of chiral ILs containing a specific functional group through the oriented design of cations and anions. Having the advantages of both ionic liquid and chiral substances, chiral ionic liquid can be used as chiral solvent or chiral inducer, which has great potentials applied in the area of chiral synthesis, chiral separation, chiral catalyst and so on.In this paper, high performance liquid chromatography method using on Chiralpak AD-H chiral column has been developed for the separation of liarozole, lansoprazole and miconazole enantiomers. In the next place, three RTILs were synthesized. Their structures and physics-chemical properties were preliminary studied. In this foundation, enantioseparation of omeprazole, pantoprazole and cetirizine by CE using ionic liquids as background electrolyte (BGE) or modifier was described. The separation mechanism was also discussed. 1. Studies on the enantiomeric separation of Liarozole, Lansoprazole and MiconazoleLiarozole, Lansoprazole and Miconazole are all administered as racemates. High performance liquid chromatographic (HPLC) methods have been used for the direct resolution of the three chiral drugs on a Chiralpak AD-H chiral column. The influences of organic solvent, the concentration of the acid and base, the flow rate and the column temperature on the enantiomeric separation were investigated. And the enantiomeric separation was optimized. The three drugs enantiomers can be separated completely. The proposed method was established to be simple, rapid and reproducible.2. Studies on the synthesis of three chiral (achiral) ion liquidsThe chiral groups could be lead to ionic liquid to obtain chiral ionic liquids. This article synthesized ephedrine and amino acids ion liquids used the natural source of ephedrine and chiral amino acids with simple methods, at the same time Imidazole and tetrafluoroborate salt as raw materials we synthesized imidazole achiral ion liquid with oversimplified synthesized. Their structures were determined by nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectrometry (MS) spectra data. Their physics-chemical properties were preliminary studied and analysised by ultraviolet spectra (UV) and solubility.3. Ionic liquids as chiral selectors for separation of three drugsIonic liquids are composed entirely by ion and both in CE as chiral selector also as and electrolyte which further improve the separation performance of the CE. But there are few reports about using ionic liquids as chiral selectors in CE. CE methods have been developed for the enantiomeric separation of omeprazole, pantoprazole and cetirizine with Ephedrine ion liquid as the chiral additive under non-aqueous mode. The effect of some factors such as the concentration of ion liquid, column temperature, voltage and the kind and concentration of organic modifier on the enantiomeric separation were investigated. And the three chiral drugs were separated perfectly on the optimized conditions.
Keywords/Search Tags:chiral drugs, chiral stationary phases, ion liquid, enantiomeric separation, HPLC, capillary electrophoresis
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