HPLC手性固定相法分离5个康唑类药物对映体

Enantiomeric separation of five conazole drugs with chiral HPLC

目的:建立高效液相色谱手性固定相法拆分硫康唑、咪康唑、益康唑、异康唑和芬替康唑5个抗真菌药物对映体,探讨其分离机制,得到理想的拆分条件。方法:采用Chiralcel OJ-H手性色谱柱,检测波长为230 nm,柱温为25℃,流速为1.0 mL·min-1,进样量为20μL;以保留时间(t)、选择因子(α)和分离度(R)为指标,考察流动相中有机改性剂的种类(乙醇、异丙醇)及其占比等对5个药物对映体分离的影响。硫康唑、咪康唑和异康唑流动相组成为正己烷-乙醇(80∶20,v/v);选择分离益康唑流动相组成为正己烷-乙醇(60∶40,v/v);选择分离芬替康唑流动相组成为正己烷-乙醇(20∶80,v/v)。结果:硫康唑、咪康唑、益康唑、异康唑和芬替康唑5个药物的对映体均达到完全分离,分离度分别为2.83、4.23、5.96、4.61、4.84。结论:Chiralcel OJ-H手性色谱柱HPLC法对这5个康唑类药物选择性良好,可用于其对映体的手性分离。

Objective:To develop a high performance liquid chromatography with chiral stationary phase method for enantiomeric separation of five antifungal drug enantiomers including sulconazole,miconazole,econazole,isoconazole and fenticonazole,and also to investigate the chiral recognition mechanisms. Methods:HPLC method was adopted. Chiralcel OJ-H chiral column was selected. Detection wavelength was set at 230 nm;column temperature was 25 ℃;flow rate was 1.0 mL·min-1;The injection volume was 20μL. Using retention time,selective factors and separation rate as indexes,the influence of type and ratio of organic modifiers(ethanol,isopropanol)on the separation of 5 kinds of enantiomers in mobile phase were investigated. The mobile phase for separation of sulconazole,miconazole and isoconazole was a mixture of n-hexane and ethanol(80∶20,v/v),while mobilephase for separation of econazole,a mixture of n-hexane and ethanol(60∶40,v/v) and mobile phase for separation of fenticonazole,a mixture of n-hexane and ethanol(20∶80,v/v). Results:Under the above condition,5 kinds of drug enantiomers were separated completely,with the separate rate of 2.83,4.23,5.96,4.61,4.84,respectively. Conclusions:Established Chiralcel OJ-H chiral column-HPLC is selective for these 5 kinds of conazole drugs and can be used for the chiral separation of the enationmers.