山莨菪碱和阿托品毛细管电泳手性拆分研究

Study on the Enantiomeric Separation of Anisodamine and Atropine by Capillary Electrophoresis

为分离生物碱氢溴酸山莨菪碱和盐酸阿托品手性对映体,探讨手性分离机理,在区带毛细管电泳模式下,以环糊精和环糊精衍生物为手性选择试剂,考察手性试剂的种类、浓度及缓冲溶液pH值和其它电泳条件对手性拆分效果的影响.结果显示,分离电压为-15kV,检测波长为200nm,缓冲溶液组成为含5%高磺化环糊精(HS-α,β,γ-CD)的50mmol.L-1磷酸盐-三乙胺溶液(pH2.5)为最佳实验条件.其中HS-γ-CD基线拆分了山莨菪碱中2个手性碳原子的2对对映体,HS-β-CD分离了2种物质并基线拆分了山莨菪碱和盐酸阿托品中1个手性碳原子的1对对映体.因此,对于氨类碱性手性药物,高磺化环糊精比未衍生化环糊精和羟丙基环糊精的拆分效果好,而酸性条件下,高磺化环糊精与叔胺类物质间手性拆分作用除了空间匹配、氢键作用外,还存在静电引力作用.

To separate the chiral enantiomers of hydrobromide Anisodamine and hydrochloric Atropine and to discuss the chiral separation mechanism of cyclodextrins. With capillary zone electrophoresis, cyclodextrins and derivational cyclodextrins are used as the chiral selectors, the effects of the chiral agent＇s style, buffer composition and pH on the chiral separation are investigated. Two pairs of chiral enantiomers of Anisodamine are baseline separated using HS-γ-CD as the chiral selectors, and one pair of chiral enantiomers of Anisodamine and Atropine are baseline separated using HS-β-CD as chiral selector in the following optimum conditions, 5% highly sulfated cyclodextrins in 50 mmol · L^-1 triethylammonium phosphate solution（pH 2.5）, --15 kV running voltage and 200 nm on-line detection. The performance of the enantiomeric resolution is better with highly sulfated cyclodextrins than underivational cyclodextrins and hydroxylpropyl cyclodextrins for amino basic medicament. In acid solution, there is the static gravitational action in addition to space matches and hydrogen bonding between highly sulfated cyclodextrins and the amine drugs.