New Synthesis Method Of Carboxymethyl Cyclodextrin And Application To Separation Of Chiral Drugs

Metoprolol and bisoprolol were separated by capillary electrophoresis(CE) using self-synthesized carboxymethyl-β-cyclodextrin as chiral selectors. This paper has been divided into four chapters, whose main contents are as follows:Chapter 1:Introduction. The purpose and significance of separation of chiral compounds was briefly discussed. The common methods for separation of chiral pharmaceuticals were summarized in this part, including pure chemical, crystal, chromatographic and enzymatic separation. It was paid attention to that the classification of chiral selectors used in capillary electrophoresis and theirs recent development, and the detailed information on the Cyclodextrin (CD) concerning its structure, properties, the advantages of chemically modifiedβ-CD, and possible tendency in modifiedβ-CD was also presented.Chapter 2:CD and its chemical modifiers as chiral selector are commonly used in CE. Compared with pure CD, carboxymethyl CD has a high solubility in water and has a strong interaction with positively charged chiral compounds. But its relatively higher price in the market restricted its usage. Ultrasound-assisted reaction method was employed to replace the traditional preparation. The preparation period was significantly shortened from traditional 18h to current 1h. The optimum preparation conditions were obtained after studying experimental conditions such as the ultrasonic reaction time and the location of the reaction vessel in ultrasonic bath. The product was evaluated and tested by the degree of substitution, IR, NMR and elemental analysis.Chapter 3:In this part, the chiral separation of metoprolol and bisoprolol was studied by CE with CM-β-CD as chiral selector. To optimize separation conditions, the influences of CD type, CM-β-CD concentration, pH of buffer solution, applied voltage and operation temperature were systematically investigated.Chapter4:Enantiomers can be separated in CE due to the differences in binding constrants between enantiomers and cyclodextrins. Based on the relation between the electric mobilities of enantiomers and the concentration of cyclodextrins in background electrolyte solution, binding constant can be estimated. Since the examined pH range is less than 8, phenol can be regarded as neutral compound, and electroosmotic flow velocity was therefore calculated from the migration time of phenol. The binding constants of enantiomers were estimated by a nonlinear regression on the basis of relationship between electrophoretic mobilities and CDs concentrations in background electrolyte solutions.