College of Pharmaceutical Science, Zhejiang University of Technology, Huzhou, 313200, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Huzhou, 313200, China.
J Chromatogr A. 2023 Aug 30;1705:464185. doi: 10.1016/j.chroma.2023.464185. Epub 2023 Jun 29.
This study reports a successful enantioseparation of two antifungal drugs, Ketoconazole and Voriconazole, using countercurrent chromatography (CCC) with synthesized sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as chiral selector. Two biphasic solvent systems composed of dichloromethane: 0.1 mol L of phosphate buffer solution (pH 3.0) (1:1, v/v) and n-hexane: ethyl acetate: 0.1 mol L phosphate buffer solution (pH 3.0) (1.5:0.5:2, v/v/v) were selected. Influence factors were investigated, including degree of substitution of SBE-β-CD, concentration of SBE-β-CD, equilibrium temperature, and pH of aqueous phase. Under optimized separation conditions, a large enantioseparation factor of α ≥ 3.26 and a high peak resolution R= 1.82, was achieved for enantioseparation of Voriconazole by countercurrent chromatography, and purity of two azole stereoisomers collected from CCC separation reached 98.5%, as determined by HPLC. Molecular docking was employed to investigate the formation of inclusion complex.
本研究报告了使用合成的磺丁基醚-β-环糊精（SBE-β-CD）作为手性选择剂，通过逆流色谱（CCC）成功分离两种抗真菌药物酮康唑和伏立康唑。选择了由二氯甲烷：0.1 mol/L 磷酸盐缓冲液（pH 3.0）（1:1，v/v）和正己烷：乙酸乙酯：0.1 mol/L 磷酸盐缓冲液（pH 3.0）（1.5:0.5:2，v/v/v）组成的两种双相溶剂体系。考察了影响因素，包括 SBE-β-CD 的取代度、SBE-β-CD 的浓度、平衡温度和水相 pH 值。在优化的分离条件下，通过逆流色谱实现了伏立康唑的大对映体分离因子α≥3.26和高峰分辨率 R=1.82，并且从 CCC 分离收集的两种唑类立体异构体的纯度达到 98.5%，通过 HPLC 确定。采用分子对接研究了包合物的形成。
