HPLC手性固定相法分离5个康唑类药物对映体

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20 μL；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.

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