二氢吡啶钙拮抗剂马尼地平和西尼地平对映体的手性拆分研究

Study on the chiral resolution of dihydropyridine calcium antagonists manidipine and cilnidipine enantiomers

目的:建立二氢吡啶类钙拮抗剂马尼地平和西尼地平对映体的手性分离方法。方法:在OD-H手性柱上分别考察了在流动相正己烷中,不同的醇类添加剂以及醇类添加剂的浓度对手性分离的影响。结果:当流动相为正己烷-异丙醇(95:5),流速1.0 mL·min^(-1),温度20℃时马尼地平分离度R_s为1.58;流动相为正己烷-正丁醇(92.5:7.5),流速1.0 mL·min^(-1),温度20℃时西尼地平分离度R_s为1.88。研究了空间立体结构因素对手性分离的影响,并在此基础上对其手性识别机理进行探讨。结论:本法操作简便,可用于马尼地平和西尼地平对映体的分离分析。

Objective：To establish an HPLC chiral separation method for dihydropyridine calcium antagonists manidipine and cilnidipine enantiomers.Methods：In this paper,the separation of manidipine and cilnidipine was studied on Chiralcel OD - H chiral columns.The influence of the structures of the analytes on the chiral separation was investigated. The mobile phase composition including the concentration and type of the alcohol modifiers in hexane was varied,and the influence on the retention factor（k＇） for each enantiomer,the separation factor（α） and the resolution （Rs） was studied.Results：On Chiralcel OD - H manidipine can be baseline separated R_s = 1.58 using hexane - iso-propanol（95：5） as eluent and cilnidipine can be baseline separated Rs= 1.88 using hexane - n-butanol （92.5：7.5） as eluent,at a flow rate of 1.0 mL·min^-1 and at 20℃.Then the chiral recognition mechanism were discussed.The steric fit of solute into the chiral cavity maybe the predominant factor for the chiral recognition of manidipine and cilnidipine.Conclusion：It is recommended that this simple and selective method be used for enantioseparation of manidipine and cilnidipine enantiomers.