3种含氮杂环类药物的手性色谱拆分及其制剂中对映体含量的测定  

Chiral Separation and Determination of Enantiomers of Three N-Heterocyclic Drugs in Tablets by Revered Phase High Performance Liquid Chromatography

作　　者：全思思 陈智[1] 吴学昊 汤逊尤 淮文蓓 张薇[2] 叶连宝[1] 范华均[1] 

机构地区：[1]广东药科大学药学院,广东广州510006 [2]广东药科大学基础学院,广东广州510006

出　　处：《分析测试学报》2016年第9期1167-1171,共5页Journal of Instrumental Analysis

基　　金：广东省战略性新兴产业核心技术攻关计划资助项目(2012A080800012);广东省科技发展专项基金项目(2016A040403119)

摘　　要：采用纤维素-三(4-甲基苯甲酸酯)手性固定相,利用反相高效液相色谱法研究了奥沙西泮、吡格列酮和罗格列酮3种含氮杂环类手性药物的色谱拆分行为。考察了流动相组成、p H值和柱温对3种药物对映体分离的影响,并对其拆分机理进行了探讨。结果表明,采用甲醇-水为流动相,通过添加醋酸或氨水调节p H值和控制柱温,可使3种药物的对映体得到完全分离(RS>1.5),根据各自优化的色谱条件建立了这3种手性药物对映体的分析方法,并应用于其制剂的含量测定,方法简单、可靠。A novel method for the determination of enantiomers of three N-heterocyclic drugs was developed by revered phase high performance liquid chromatography using cellulose-tris-（4-methylbenzoate） as chiral stationary phase（CSP）. Enantioseparation of oxazepam,pioglitazone and rosiglitazone on the CSP were performed by using mixture of methanol and water as mobile phase. Effects of methanol-water ratio,pH value and temperature on chiral separation of three drugs were investigated,respectively.The results showed that their enantiomers were separated on the CSP with methanol-0.01% acetic acid solution（50∶50） at 25 ℃ under pH 6.0 for oxazepam, methanol-0.01% ammonia solution（60∶40） at 30 ℃ under pH 8.0 for pioglitazone,and methanol-0.01% ammonia solution（65∶35） at 40 ℃ under pH 8.0 for rosiglitazone,respectively. The mechanism of racemic resolution for three drugs was discussed.The proposed method was successfully applied in the determination of three drugs enantiomers in commercial tablets,with recoveries and relative standard deviations（RSDs） of 94.6% -106.2% and 0.07%-1.0%,respectively.It was proved to be simple,reliable and accurate.

关 键 词：反相高效液相色谱法 含氮杂环类药物 纤维素-三(4-甲基苯甲酸酯) 手性固定相 手性色谱拆分 

分 类 号：O657.72[理学—分析化学] TQ460.72[理学—化学]