【作者】 姜军坡；

【导师】 夏之宁；

【作者基本信息】 重庆大学 ， 生物化工， 2007， 硕士

【摘要】 可溶性淀粉和糊精是新型的毛细管电泳手性选择剂,对药物对映体具有广泛的手性选择性。虽然学术界对可溶性淀粉和糊精的手性分离机理已有初步的探索,但在药物毛细管电泳手性分离分析中的应用尚少。本论文以可溶性淀粉和糊精作为毛细管电泳手性选择剂,对伯氨喹对映体、苯海索对映体和布洛芬对映体进行了手性分离,并对其手性分离机制进行初步探讨。以未涂敷毛细管为分离通道,可溶性淀粉和糊精为手性选择剂,在磷酸盐缓冲液中分别对伯氨喹对映体、苯海索对映体、布洛芬对映体进行了手性分离研究。考察了可溶性淀粉和糊精浓度、缓冲溶液pH值、缓冲溶液离子强度、运行电压以及有机添加剂等对分离的影响。结果表明,手性选择剂的浓度和pH对分离的影响最大。药物对映体的分离度随着手性选择剂的浓度增大而增大,但是如果手性选择剂浓度过高则会导致缓冲液粘度的增大,从而使分离度的下降。pH对对映体分离的影响是极为重要的,只有在合适的pH范围内才能实现对映体的分离。在优化的实验条件下,三种药物对映体都达到了基线分离,并确定了伯氨喹对映体和苯海索对映体的线性检测范围。结果表明,伯氨喹对映体和苯海索对映体在线性检测范围内的线性关系良好,线性相关系数在0.9093以上。指认了布洛芬对映体。结果表明,(+)-布洛芬对映体和可溶性淀粉或糊精的相互作用更强。综合研究结果,论文探讨了可溶性淀粉和糊精浓度可能的手性识别机理。对进一步阐明详细的识别机理具有一定的意义,同时也为预测此类手性选择剂对新手性药物的分离可能性提供了基础。更多还原

【Abstract】 Amylose and dextrin were new kinds of chiral selectors in chiral capillary electrophoresis. They have shown wide enantioselectivity to chiral drugs. Although reports about amylose and dextrin as chiral selector have been made, but the application of amylose and dextrin as chiral selector in chiral capillary electrophoresis was limited. In this thesis, amylose and dextrin were used as chiral selectors for the chiral separation of primaquine enantiomers, benzhexol enantiomers and ibuprofen enantiomers. The principle of separation was discussed.With an uncoating capillary as the separation channel, the chiral separations of three kinds of enantiomers were researched in phosphate buffer solution using amylose and dextrin as chiral selectors. The effects of the concentration of amylose and dextrin, pH of buffer solution, the concentration of phosphate, the applied voltage and the addition of organic reagent on the separation were discussed. It can be concluded from the results that the concentration of amylose and dextrin and pH of buffer solution were the most important factors. Generally speaking, the resolution of pharmaceutic enantiomers increased whem the concentration of amylose and dextrin increased, but the resolution would decrease when the concentration of amylose and dextrin were so high that the viscidity of buffer solution were increased greatly. pH of buffer solution was the vital factor to the resolution. The resolution of pharmaceutic enantiomers achieved only in an appropriate pH range.The base line resolution of three kinds enantiomers achieved under optimized operation conditions. The linearity detection ranges were confirmed. The results shown that the linearity relations between the linearity detection ranges were good and the linearly dependent coefficient were above 0.9093. The enantiomers of ibuprofen were identified. It can be concluded from results that the interaction between (+)-ibuprofen and amylose or dextrin were higher than that between (-)-ibuprofen and amylose or dextrin.In this thesis, the probable mechanism of chiral separation of amylose and dextrin 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 amylose and dextrin as chiral selector.更多还原