The Applications Of The Cyclodextrin And Its Derivatives In Drug Analysis

For almost 30 years,all kinds of cyclodextrins(CDs) and their derivatives have been widely used in medicine,chemicals,agriculture,consumer products and the areas of biotechnology in abroad.Due to their unique structures,cyclodextrins can be formed inclusion complexes with all kinds of different polarity materials.Multiple chiml centers of cyclodextrins made the complexes with a high stereoselectivity.Therefore,they have high value in the research and application in chiral chromatography separation,even can be used in components of drugs,food additives or tobacco etc.Among them,β-CD was applicated most prevalently in the analysis for its easy preparation and low expenditure.However,the bad solubility ofβ-CD restricted its application and separation.So,the derivation of cyclodextrin was tried to modify the disadvantages and improve the applications,We synthesized severalβ-cyclodextrin derivatives firstly,and those derivatives were used as chiral selector to separate some chiral drugs by capillary electrophoresis successfully.The peaks sequence of Propranolol was assured;the reselution results obtained in the use of diffrerent chiral selectors were studied,and provide a scientific basis for the capillary electrophoresis chiral separation study in the future.Secondly,several daidzein/Different degree of substitution hydroxypropyl-β-cyclodextrin inclusion complexes were synthesized,their effects on solubilization and drug content were studied.The present paper mainly includes the following three parts:The first chapter:The applications of the cyclodextrin and its derivatives in drug analysis and their synthesis of progress were reviewed,and the features and principle of the capillary electrophoresis were introduced briefly.It was further evaluated about the influence factors of the CD-CE chiral separation:pH of the buffer solution,the type and concentration of the buffer solution, the type and concentration of CD,mixed chiral selectors,effects of applied voltage and operating temperature.The second chapter:The reaction was performed as described in the literature,β-cyclodextrin was treated with propylene epoxide in the presence of sodium hydroxide.Ten different DS HP-β-CD were synthesized by changing the amount of alkali,and the DS was calculated respectively.Six inclusion complexes of daidzein and HP-β-CD with suitable interval degree of substitution were prepared.The binary systems of daidzein / HP-β-CD were determined by infrared spectroscopy(IR), X-ray diffractometry(XRD),and UV/Vis spectroscopy.Several methylatedβ-cyclodextrins and carboxymethyl-β-cyclodextrin were synthesized according to the literature methods,and the structures were characterized by ~1HNMR.The third chapter:In this thesis,β-cyclodextrin derivatives synthesized in the previous chapter were applied in drug analysis.Five chiral molecules were successfully separated by the capillary electrophoresis with carboxymethyl-β-cyclodextrin as a chiral selector firstly,good results were obtained by optimizing conditions of separation.And the peaks sequence of Propranolol was assured by changing the proportion of the enantiomers' concentration.Next,the methylatedβ-CDs in different substitution positions in chiral separation were compared,and the possible reason of the difference in separation was studied.Finally,there is a conclusion about the progress of the paper.