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Chiral Ligand-exchange Chromatography For Separation Of Isomers Of Chiral Drugs And The Mechanism Study

Posted on:2007-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:S Y SunFull Text:PDF
GTID:1104360185989145Subject:Drug analysis
Abstract/Summary:PDF Full Text Request
Chiral ligand-exchange chromatography (CLEC) is one of the basic chromatography method for enantiomer separation, in which chiral ligands and metal ions are two essential elements to determine the chiral selectivity. In this study enantiomers of some chiral drugs and amino acids were separated, by chiral coated phases (CCP) and chiral mobile phases (CMP). Various factors affecting the chromatographic behaviour and chiral selectivity and mechanism were studied. The stability of complexes between chiral ligands and metal ions (Fe2+,Co2+,Ni2+,Zn2+,Cu2+,Pb2+,Hg2+) and the critical role in chiral separation were studied by using CCP and CMP methods.1. The isomers of Octahydroindole-2-carboxylic acid (Oic) and Benazepril Hydrochloride(BNP) were separated and assayed by using CMP. The factors such as metal ions, ligands, ion-pair reagents, pH, column temperature and organic modifiers affecting the retention and resolution were studied. The isomers of Oic were separated on Zorbax bonus-C8 column with the mobile phase of 20% acetonitrile and 80% aqueous solution (pH 6.0) containing 1.0 mmol/L Cu (II) acetate, 2.0 mmol/L L-phenylalaninamide (L-PheA) and 5.0 mmol/L PIC-B. The isomers of BNP were separated on Diamonsil C18 column with the mobile phase of 60% methanol and 40% aqueous solution (pH 6.0) containing 1.0 mmol/L Cu (II) acetate, 2.0 mmol/L Vitasweet (APM) and 2.0 mmol/L PIC-B. Baseline separation of the isomers of Oic and BNP were obtained under these chromatographic conditions, and a linear relationship between peak area and concentration was achieved in the range of 10~ 300μg·mL-1 and 5~300 μg·mL-1, respectively.The effect concentration of ion-pair reagent on retention factors and resolution of amino acids in CMP was studied. The results indicated that the retention time of amino acids especially D-amino acids were increased when PIC-B8 were added in mobile phase.2. Some chiral ligands deriving from amino acids, N-(n-dodecyl)-L-hydroxyproline...
Keywords/Search Tags:Chiral ligand-exchange chromatography (CLEC), chiral drugs, chiral coated phases (CCP), chiral mobile phases (CMP), chiral ligands and metal ions
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