CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory of Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
J Sep Sci. 2024 Jun;47(12):e2400190. doi: 10.1002/jssc.202400190.
An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as a chiral selector in high-speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two-phase solvent system consisting of n-hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE-β-CD) (1.5:0.5:2, v/v/v). A fast and predictable scale-up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11-fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high-performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale-up process and attaining continuous separation of chiral drugs.
建立了一种使用磺丁基醚-β-环糊精（SBE-β-CD）作为手性选择剂的高效方法，用于高速逆流色谱（HSCCC）连续分离伏立康唑对映异构体。使用由正己烷/乙酸乙酯/100mmol/L 磷酸盐缓冲液（pH=3.0，含 50mmol/L SBE-β-CD）（1.5:0.5:2，v/v/v）组成的两相溶剂系统进行分离。使用分析型 DE-HSCCC 仪器实现了快速和可预测的放大过程。随后将优化的参数应用于制备型 Tauto-HSCCC 仪器，在分离时间和对映体纯度方面保持一致，通量提高了 11 倍。制备型 HSCCC 成功分离了 506mg 外消旋体，高效液相色谱分析证实对映体纯度超过 99%。该研究提出了一种有效的方法来预测 HSCCC 放大过程，并实现手性药物的连续分离。
