抗痴呆症药中加兰他敏对映异构体的毛细管电泳分离及药物质量控制  

Enantiomeric Separation of Galantamine in Drug for Alzheimer's Disease and Its Quality Control by Capillary Electrophoresis

作　　者：颜流水[1] 赵基源[1] 罗国安[1] 孙命[1] 王义明[1] 杨学东[1] 

机构地区：[1]清华大学化学系,北京100084

出　　处：《高等学校化学学报》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

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 Alzheimers 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-guest 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-guest 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.

关 键 词：抗痴呆症药 加兰他敏 对映异构体 毛细管电泳分离技术 药物质量控制 药代动力学 Α-环糊精 键合常数 

分 类 号：R971[医药卫生—药品] R917[医药卫生—药学]