The enantioseparation of eight psychoactive drugs has been firstly performed on a coated cellulose‐based chiral stationary phase (Chiralcel OJ‐H). To obtain optimum separation conditions, the influences of alcohol modifiers and basic/acidic additives have been studied. As a result, except for the partial separation of oxybutynin enantiomers, the other seven drug enantiomers, including mirtazapine, sulpiride, promethazine, citalopram, oxazepam, donepezil, and cyamemazine, have been completely separated. Additionally, for gaining a better insight into the chiral recognition mechanisms, molecular docking was carried out using the Autodock software. Herein, binding energy and conformations of the chiral stationary phase complexes were provided, and it was found that the distinction in enantiomeric conformation determined the number and strength of intermolecular interactions between analytes and chiral stationary phase which resulted in the difference in binding energies of two enantiomers, and ultimately led to the different migration. These modeling results were in accordance with the observed enantioseparation results in high performance liquid chromatography experiments. At last, chiral separation mechanisms have been discussed in detail, and it has been confirmed that hydrogen bond, π–π, hydrophobic interactions, and some special interactions synergistically contributed to the enantioseparation of psychoactive drugs.

中文翻译：

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八种精神活性药物在包覆多糖手性固定相上的对映体分离和分子建模研究。


八种精神活性药物的对映体分离首次在涂覆的纤维素基手性固定相 (Chiralcel OJ-H) 上进行。为了获得最佳分离条件，研究了醇改性剂和碱性/酸性添加剂的影响。结果，除奥昔布宁对映体部分分离外，米氮平、舒必利、异丙嗪、西酞普兰、奥沙西泮、多奈哌齐、氰胺马嗪等7种药物对映体均已完全分离。此外，为了更好地了解手性识别机制，使用 Autodock 软件进行分子对接。本文提供了手性固定相复合物的结合能和构象，发现对映体构象的差异决定了分析物与手性固定相之间分子间相互作用的数量和强度，从而导致两种对映体的结合能不同，最终导致不同的迁移。这些建模结果与高效液相色谱实验中观察到的对映体分离结果一致。最后，详细讨论了手性分离机制，并证实氢键、π-π、疏水相互作用和一些特殊相互作用协同促进精神活性药物的对映体分离。