伏立康唑对映体HPLC手性拆分及分析

目的: 建立伏立康唑对映体HPLC手性分离及分析方法。 方法: 以β-CD及其衍生物为流动相手性添加剂,探讨β-CD衍生物类型及浓度、流动相中有机相体积分数、色谱柱固定相类型等因素对伏立康唑对映体HPLC手性拆分效果的影响,在此基础上,建立伏立康唑对映体的HPLC分析方法,并进行方法学考察。 结果: β-CD衍生物中,SBE-β-CD适宜作为伏立康唑对映体HPLC手性拆分添加剂,以甲醇-水(45: 55)为流动相,磷酸二氢钾浓度为15 mmol·L^-1,SBE-β-CD浓度为10.0 mmol·L^-1时,伏立康唑对映体在C₈及C₁₈固定相上均能得到有效拆分。在上述条件下,以Hypersil C₁₈色谱柱(4.6 mm×150 mm,5 μm)分析伏立康唑对映体,流动相流速为1.0 mL·min^-1,伏立康唑对映体能实现基线分离,伏立康唑浓度在31.2~156 μg·mL^-1范围内,浓度与峰面积呈良好线性关系(R²=0.9998),伏立康唑加样回收率大于98%,稳定性及重现性RSD分别为0.77%,0.67%。 结论: 建立了一种伏立康唑对映体的手性拆分和分析方法,可为伏立康唑的分离与分析提供借鉴。

Objective: To establish an HPLC chiral separation and analysis method of voriconazole enantiomers. Methods: Using β-CD and its derivates as chiral additives of mobile phase,the influences of the type and concentration of cyclodextrins,mobile phase ratio,and type of column stationary phase on the chiral separation were investigated.Then an HPLC analysis method of voriconazole enantiomers was established and methodologically discussed. Results: Sulfobutylether-β-cyclodextrins(SBE-β-CD),as the chiral additive,is more suitable for HPLC separation of voriconazole enantiomers than other β-CD derivates,and voriconazole enantiomers could be effectively separated on C₈ and C₁₈ stationary phase with methanol-water(45:55)as mobile phase at the KH₂PO₄,SBE-β-CD concentrations of 15.0 mmol·L^-1 and 10.0 mmol·L^-1,respectively.Under the conditions mentioned above,the voriconazole enantiomers was base-line separated on the Hypersil ODS C₁₈ column(4.6 mm×150 mm,5 μm)at a mobile phase flow rate of 1.0 mL·min^-1.By methodological analysis,the average recovery of voriconazole was more than 98%, and the RSD values of stability and reproducibility were 0.77% and 0.67%,respectively. Conclusion: The proposed method is suitable for the chiral separation and analysis of voriconazole enantiomers by HPLC.