摘要
建立了以 α-环糊精为手性选择剂的毛细管区带电泳用于分离治疗老年性痴呆病药物加兰他敏手性异构体的方法 ,测定了加兰他敏对映体与 α-环糊精包结物的键合常数和手性识别过程的热力学参数 .通过计算机模拟构象分析 ,探讨了分离机理 .研究结果表明 ,对映异构体最大分离度为 3 .60 ,R和 S对映异构体与α-环糊精的键合常数分别为 KR- CD=3 3 .98L/ mol和 KS- CD=2 3 .90 L/ mol.将该方法用于加兰他敏原料药分析 ,分离出 1 0种结构相似的化合物 ,测得非药效成分 R型异构体含量为 0 .82 % ,测定的线性范围为0 .0 1 5～ 1 .0 mmol/ L,迁移时间和峰面积的精度分别为 0 .2 0 %和 2 .6% .
A method for capillary electrophoretic enantiomeric separation of a novel drug for Alzheimers disease, Galantamine, has been established with α-cyclodextrin as the chiral additive. General equations and data analysis approach are presented to relate molibilities to equalibrium constants in simple binding equilibria and used to determine bonding constants and thermodynamic parameters for host-vip complexation of galantamine enantiomers with cyclodextrin selector. The effects of cyclodextrin concentration and type, buffer concentration and its pH, and separation voltage were investigated. The mechanism of enantioselectivity is discussed by combining with the computer simulating conformational analysis. The maximal resolution of 3 60 was obtained . The bonding constants of host-vip complex of galantamine enantiomers with α-cyclodextrin, K_ R-CD and K_ S-CD, is 33 98 L/mol and 23 90 L/mol, respectively. The established method was successfully applied to the detect ion of the non-effective component in the raw material of galantamine. Ten structural analogues were found, and the content of R enantiomer is 0 82%. The concentration linear rang is 0 015—1 0 mmol/L with the analysis precision of 0 20% and 2 6% for the measurement of migration time and peak area, respectively. Thus, the method could be used as a rapid and reliable tool for quantity control of the drug.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2004年第2期256-260,共5页
Chemical Journal of Chinese Universities
基金
国家重大基础研究规划项目 (批准号 :G19990 5 44 0 4)资助
