几种苯甲酰胺类抗精神病药物的手性色谱拆分及其对映体含量的测定  

Chiral separation of benzamide antipsychotics and determination of their enantiomers by high performance liquid chromatography

作　　者：王李平[1] 范华均[1] 巫坤宏[1] 彭晓升[1] 江子滔[1] 臧林泉[1] 

机构地区：[1]广东药学院药科学院,广东广州510006

出　　处：《色谱》2012年第12期1265-1270,共6页Chinese Journal of Chromatography

基　　金：国家"重大新药创制"科技重大专项(2011ZX09102-001-31);广东药学院师资队伍建设基金项目(52104109)

摘　　要：采用直链淀粉-三(5-氯-2-甲基苯基氨基甲酸酯)手性固定相(CSP),以0.1%二乙胺正己烷和0.1%二乙胺乙醇为流动相梯度洗脱,以舒必利、阿米舒必利和莫沙必利为目标物,利用高效液相色谱法研究了这3种苯甲酰胺类药物的手性色谱分离行为。分别考察了流动相组成、添加剂及柱温对3种药物对映体分离的影响,从热力学和结构上探讨了色谱拆分的机理。结果表明:在优化的色谱条件下,舒必利、阿米舒必利和莫沙必利对映体的分离度Rs>1.5;计算了3种药物对映体的色谱保留因子k和分离因子α,以及与CSP相互作用的热力学函数,其相互作用大小依次为舒必利>阿米舒必利>莫沙必利。已将该方法成功地应用于上述3种药物片剂和血清中其对映体的测定,方法简便、准确、可靠。A new method of the chiral separation of three drugs such as sulpiride,amisulpride and mosapride was developed on the chiral stationary phase of amylose-tris-（5-chloro-2-methyl-phenylcarbamate）（ACMPC） by high performance liquid chromatography.The chromatographic behaviors of enantiomers of the three drugs were investigated in the mobile phases consisted of ethanol and n-hexane（containing 0.1%（v/v） diethylamine）.The chromatographic conditions including the composition of the mobile phase,additives and temperature were further optimized for the chiral separation.The mechanism of racemic resolution for the mentioned drugs is discussed thermodynamically and structurally.The results indicated that these three chiral drugs could be separated on an ACMPC column under the optimum conditions,and their chiral resolutions were improved up to more than 1.5.The chromatographic parameters such as the retention factor k,separation factor α are presented,and the thermodynamic functions were calculated for the separation of the enantiomers of the three drugs.The method has been successfully applied to the determination of the enantiomers of the three drugs in tablets and blood serum.It is simple,reliable and accurate.

关 键 词：高效液相色谱法 舒必利 阿米舒必利 莫沙必利 药物 手性拆分 

分 类 号：O658[理学—分析化学]