A twin‐column recycling chromatography with solvent gradient was developed to isolate the minor impurities in the drugs. Two columns were connected through two 6‐port valves, and the solute band was diverted from one column into another by switching the valves. During the circulation of the solute band, a modifier was constantly added to the middle between the two columns so that the eluotropic strength of the downstream liquid was reduced. Thereby, the front of the band moved slower than the tail, bringing about a band compression effect to offset the band broadening so as to improve the separation and enhance the concentration of fraction without reducing the feeding amount. Such modified scheme was successfully used to purify a proprietary intermediate, displaying great advantages over the conventional scheme without solvent gradient in terms of recovery and fraction concentration. © 2018 American Institute of Chemical Engineers AIChE J, 65: 702–711, 2019

中文翻译：

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具有溶剂梯度的双柱循环色谱法，可增强对次要杂质的分离

开发了一种具有溶剂梯度的双柱再循环色谱法，以分离药物中的微量杂质。两根色谱柱通过两个六通阀连接，并且通过切换阀将溶质带从一根色谱柱转移到另一根色谱柱。在溶质带的循环过程中，不断在两根塔之间的中间添加改性剂，从而降低了下游液体的溶电强度。因此，条带的前部移动得比尾部慢，从而产生了条带压缩效果以抵消条带展宽，从而在不减少进料量的情况下改善了分离并提高了馏分的浓度。此类修改后的方案已成功用于纯化专有中间体，在回收率和馏分浓度方面，与没有溶剂梯度的常规方案相比，显示出极大的优势。©2018美国化学工程师学会AIChE J，65：702–711，2019