手性流动相添加法拆分酮康唑外消旋体

采用C18反相色谱柱,利用在流动相中加入手性选择剂的方法实现酮康唑对映体的拆分。研究了手性选择剂的种类及浓度、流动相pH值、甲醇比例和柱温等因素对酮康唑手性分离的影响,结果表明磺丁基-β-环糊精可以使酮康唑对映体完全分离,最后选择的流动相组成为甲醇-0.02 mol/L磷酸二氢钠(体积比为60∶40,含0.02%三乙胺和1.0 mmol/L磺丁基-β-环糊精,用稀磷酸调节pH值到3.00)。酮康唑对映体在6 min内得到基线分离,分离度为2.05。方法简便,分离效果好,对酮康唑对映体的拆分具有应用价值。

Separation of ketoconazole enantiomers using high performance liquid chromatography with chiral mobile phase additives

A simple and effective method for the separation of ketoconazole enantiomers was developed using the chiral mobile phase additive on a C18 reversed-phase column. Several β-cyclodextrins were investigated as chiral mobile phase additives separately. The results showed that ketoconazole enantiomers were well separated by only adding sulfobutyl ether-β-cyclodextrin （SBE-β-CD） into the mobile phase. Excellent enantioseparation was achieved with the mobile phase composed of methanol-0.02 mol/L NaH2PO4 (60∶40, v/v, containing 1.0 mmol/L SBE-β-CD and 0.02% triethylamine, at pH 3.00 adjusted with phosphoric acid aqueous solution). The flow rate was 1.0 mL/min. The detection wavelength was set at 225 nm and the column temperature at 30 ℃. Under the optimized conditions, the resolution of ketoconazole enantiomers was 2.05.