Highly efficient chiral separation of amlodipine enantiomers via triple recognition hollow fiber membrane extraction

- Robust and stable molecularly imprinted hollow fiber membranes were prepared.
- Triple recognition based on imprinted membrane and dual chiral additives was achieved.
- A selectivity factor for enantioseparation of (S)-amlodipine reached 1.98.
- The cross-flow experiment provided a potential large-scale production process.

In this study, a triple recognition chiral extraction process has been developed to separate (S)-amlodipine from racemic raw medicine, based on the combination of molecularly imprinted hollow fiber membrane and cross-flow biphasic recognition extraction. The chiral separation process was operated in a dismountable hollow fiber module coated with molecularly imprinted polymer, and the cross-flow extraction was applied with d-tartaric acid in feed phase and sulfobutyl ether-β-cyclodextrin in stripping phase. The synergistic effect of molecularly imprinted polymer and dual chiral additives was investigated, and excellent enantioseparation ability with a selectivity factor of 1.98 was obtained. Mathematical model of S/R = 0.598e0.150NTU for racemic amlodipine separation by molecularly imprinted hollow fiber membrane extraction was established. The optical purity for amlodipine is up to 90% when 4 hollow fiber membrane modules of 25 cm in length in series are used. The triple recognition process strongly enhanced the separation selectivity; therefore it may bring about the potentially application for large-scale production of pure enantiomeric compound.