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Synthesis Of β-Cyclodextrin Derivatives And Application For Nonaqueous Capillary Electrophoresis

Posted on:2008-02-18Degree:MasterType:Thesis
Country:ChinaCandidate:W G XingFull Text:PDF
GTID:2121360212993169Subject:Chemical processes
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Chirality is a universal phenomenon , especially in Pharmaceuticals,analytical chemistry and biological molecules. The separation enantiomer of drugs is an important subject of research in the Analysis Chemistry field. Because of the similar Physico-Chemical properties of two enantiomers , the separation becomes more difficult. Capillary electrophoresis ( CE ) has manifested its versatility and potential in the separation of chiral drugs, because of its high efficiency, rapid analysis, low cost, wide variation of separation modes, low pollution of environment, wide range of application etc.Common CE method generally is finished in aqueous medium, and as a result hydrophilic analyte is often required during the analysis procedure.Although solubility of analyte could be improved by adding surfactants and organic solvents in aqueous medium, it is required that the analyte has some solubility in water. This limits the scope of the kinds of analytes. Since Walbroehl and Jorgenson successfully separated five quinoline—type compounds in pure acetonitrile(ACN) applying a tetraethylammonium perchlorate /hydrochloric acid electrolyte in 1984, nonaqueous capillary electrophoresis (NACE), as a complement technique of CE expanded its application to many fields.Successful chiral separation lies in choosing accurate chiral selector , current research is still focus on finding and synthesizing new chiral selectors. Cyclodextrins (CDs) including native and derivatized CDs are among the widely used chiral additives in CE. However, there are some limits to the native CDs in their solubility and physico-chemical properties for chiral separation.CD derivatives exhibit different properties compared to the native ones in the following:1.Improved solubility;2.Possibility for different bonds with analytes that can improve the inclusion-complexation;3. The charged CDs can separate uncharged and charged chiral drugs. So the chiral separation using CDs derivatives is one of the challenging subjects.In chapter one, the development of chiral separation by CE and the basic theoy of nonaqueous capillary electrophoresis were reviewed, including theoretical studies, applications and different operating models.The chiral selector, electrolyte and pH~* in NACE were also reviewed.β—CD was modified on the 6 hydroxyl position in this thesis. Two modified 3—CD were synthesized to be used as the chiral selectors to separate 10 chiral drugs in NACE.The effects of organic solvent, the electrolytes, the pH of the buffer, the concentrations of the CD derivatives were investigated.6—0—( 2—Hydroxybutyl )—β—CD was synthesized, 6 chiral drugs, such as Propranolol (Rs = 2.26) , Anisodamine(Rs = 2.31) , Promethazine(Rs=2.42), Ketoconazole(Rs=2.56), Benzhexol (Rs = 3.38), Fenfluramine(Rs = 3.04), were separated , while only 3 chiral drugs such as Ketoconazole(Rs = 0.94), Promethazine (Rs = 1.15), Anisodamine(Rs= 1.22), were separated byβ-CD and 4 chiral drugs such as Propranolol (Rs= 1.83), Anisodamine (Rs=1.92), Promethazine (Rs = 1.48) ,Ketoconazole(Rs= 1.56) ,were separated by HP-β-CD.We demonstrated the calculating the ability of the 6—0—( 2—Hydroxybutyl)—β—CD as a chiral selector is better than of theβ-CD and 2-HP-β-CD.2—hydroxypropyltrimethylammonium salt ofβ-CD was synthesized.The following 4 acidic drugs such as Naproxen (Rs=2.13) , Ofloxacin (Rs = 1.52), Ibuprofen (Rs=1.87), Warfarin (Rs=1.68) were separated.While this 4 chiral drugs were not separated byβ—CD and 2—HP—β—CD in the same condition. We demonstrated the calculating the ability of the 2—hydroxypropyltrimethylammonium salt ofβ—CD as a chiral selector is better than of theβ-CD and 2-HP-β—CD.
Keywords/Search Tags:cyclodextrin derivatives, nonaqueous capillary electrophoresis, chiral drugs separation
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