Direct separation of naftopidil enantiomers was obtained with teicoplanin-bonded stationary phase in the polar organic mode.The effects of the concentration and the ratio of triethylamine and glacial acetic acid,temperature and the flow rate on retention and enantioseparation were investigated.Interactions between R/S-naftopidil and teicoplanin were studied by a software-Molecular Operation Environment (MOE).Chiral separation mechanisms were studied with the combination of thermodynamics and molecular simulation.The results indicated that the values of resolution (Rs) increased with decreasing concentration of triethylamine and acetic acid.Best resolution was achieved when the ratio of triethylamine and acetic acid was 1 ∶ 1.In addition,the resolution decreased with the increase of temperature and flow rates.The optimal separation condition of Naftopidil on Chirobiotic T column was achieved using methanol-triethylamine-acetic acid (100∶0.002∶0.002,V/V) as the mobile phase at the flow rate of 1 mL/min and the temperature of 30 ℃.The value of Rs was 2.0 and the theoretical plates were 5100.The results of thermodynamics and molecular simulation both indicated that the main driving forces of chiral separation included hydrogen bonding,steric hindrance and π-π interaction.%在极性有机相条件下用替考拉宁手性柱(Chirobitotic T)直接分离萘哌地尔对映体.考察了三乙胺、醋酸的浓度、比例及柱温、流速对拆分的影响.应用Molecular operation Environment(MOE)软件模拟R/S-萘哌地尔与替考拉宁的相互作用,结合热力学参数探讨其分离机制.结果表明,随着甲醇中三乙胺和醋酸的浓度变小,分离度增大；三乙胺与醋酸的体积比为1∶1时,分离度最好.温度和流速的升高都会使分离度降低.优化后条件为:流动相为甲醇-三乙胺-醋酸(100∶0.002∶0.002,v/v),流速1 mL/min,柱温30℃.在此条件下,萘哌地尔对映体达到了最佳分离,分离度为2.0,理论塔板数达到5100.结合热力学参数和分子模拟结果表明,引起手性识别的主要作用力包括氢键、立体阻碍和π-π作用力.
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