1. Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation.
- Author
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Sun, Xiao, Huang, Xin‐Yi, Pei, Dong, and Di, Duo‐Long
- Subjects
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COUNTERCURRENT chromatography , *COUNTERCURRENT processes , *VORICONAZOLE , *ENANTIOMERIC purity , *HIGH performance liquid chromatography , *CHIRAL drugs - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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