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Application And Study Of The Enantioselective Separation Of Chiral Drugs By HPLC

Posted on:2005-01-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z F ZhangFull Text:PDF
GTID:1101360125454665Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
Title of the Dr. degree's Thesis: Application and Study of the EnantioselectiveSeparation of Chiral Drugs by HPLCIntroduction of the Author: Zhang Zhefeng, was born on September, 1965. Under theguidance of Prof. Zhang Lide, he was awarded the Master Degree at Hebei MedicalUniversity in 1998. Since 2001, he has been specializing in analytical chemistry to obtainDr. Degree under the guidance of Prof. Yang Gengliang at Hebei University.Abstract: In this thesis, the separation principle of CMPA methods and several kinds ofCSP such as protein and cellulose trisphenylcarbamate derivatives was investigated andthe chiral separation methods for pazufloxacin, cetirizine and other six drugs wereestablished successfully. The paper consists of the following five chapters.In chapter one, the relationship of pharmacokinetics and clinical efficient between enantiomers of chiral drugs and the current development in chiral drugs enantioselective separation technique were introduced.Chapter two studied the enantioselective separation for pazufloxacin and ketoprofen with CMPA method. The effects of the pH of mobile phase, the concentration of organic modifier and the CMPA and the RP-stationary phase on the resolution of enantiomers were investigated. Also, the chiral separation mechanism of the two CMPA methods was discussed. The HPLC chiral separation methods for pazufloxacin and ketoprofen were developed successfully.Chapter three was focused on the enantioselective separation with proteinate-CSP methods. On the base of the investigation on the structure characteristics of al- acid glycoprotein (ccl- AGP), ovomucoid (OVM) and pepsin using as CSP and the factors affecting the resolution of the enantiomers, HPLC chiral separation methods for cetirizine and amlodipine were developed successfully on the al- AGP and OVM-CSP, respectively.Chapter four: Cellulose trisphenylcarbamate derivatives-CSP method was applied for the chiral separation of the enantiomers of TED2001. The structure characteristics of cellulose trisphenylcarbamate derivatives-CSP and the factors influencing the resolutionof the enantiomers were investigated. Then an optimum condition of separating and preparing the two pairs of enantiomers of TED2001 on cellulose trisphenylcarbamate derivatives-CSP by HPLC simultaneously was established. The preparation method was simple and milligram-scale samples of enantiomer were obtained. The purity of enantiomers obtained by the method was above 98.8%. The analytical method developed is sensitive, specific and can be used for the quality control of the new drug. Also, the chiral separation methods for tamsulosin and nateglinide were established on two kinds of cellulose derivatives-CSP successfully.Chapter five is related with the determination and quality study of cefoperazone sodium and sulbactam sodium for injection by HPLC. The method for the determination of cefoperazone sodium (CPZ) and sulbactam sodium (SBT) for injection and the examination of degradates of the drug made by solvent crystallization and lyophilization method were performed. S isomer, T-1551B in CPZ and other related substances were separated simultaneously on an ODS column. The quality of the product made by solvent crystallization method is better than that of the product made by lyophilization method.
Keywords/Search Tags:Enantiomers, Chiral Drug, Enantioselective Separation, Chiral Stationary Phase, Chiral Mobile Phase Additive
PDF Full Text Request
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