Using Non-cyclic Polysaccharide As Chiral Additive For The Separation Of Citalopram Enantiomers In Capillary Electrophoresis

The separation of enantiomers by capillary electrophoresis was based on the difference of migration behavior after interaction between chiral drug and chiral selector. The most important factor in chiral separation is the selectivity of chiral selector. Non-cyclic polysaccharide, a new kind of chiral selector in capillary electrophoresis has showed wide enantioselectivity to chiral drugs. Although studies made on non-cyclic polysaccharide, few publications on chiral separation with non-cyclic polysaccharide as chiral selector in capillary electrophoresis were reported, and the kind of non-cyclic polysaccharide used as chiral selector was limited also. In this thesis, several kinds of non-cyclic polysaccharide (or disaccharide) were used as chiral selectors for the enantiomeric separation of citalopram and its intermediate, and then the effects of the length of chain and the linkage type of these polysaccharide (or disaccharide) were discussed. First, amylose was selected as chiral selector and the enantiomeric separation of citalopram enantiomers was achieved successfully. The effects on enantioseparation were investigated and the two enantiomers could be separated well. The two enantiomers were identified and the binding intensities between two enantiomers and amylose were studied. Second, dextrin was selected as chiral selector and the two enantiomers of citalopram could be separated successfully. Under the optimal operation conditions, the linear concentration range and the lowest detective concentration of citalopram were studied. The quantitative measurement of citalopram and its enantiomers were set up. This method has been applied to the content determination of R-citalopram in Escitalopram material with satisfactory result. The effects of the length of chain and the linkage type of these polysaccharide were examined further. Maltose, sucrose and glucose were selected as chiral selectors in capillary electrophoresis. In our experiment conditions, only maltose has showed chiral discrimination ability to citalopram, and sucrose and glucose did not give any separation to citalopram. The enantiomeric separation of citalopram intermediate using dextrin as chiral selector was also studied. Under the optimal operation conditions, the linear concentration range and the lowest detective concentration of citalopram intermediate were studied. The quantitative measurement of citalopram intermediate and its enantiomers were set up, which could be used for the quality control in product process. In this thesis, the probabe mechanism of chiral separation of non-cyclic polysaccharide was discussed according to the experimental results, which could give some guidance to the further study on the chiral separation of new drug enantiomers using non-cyclic polysaccharide as chiral selector.