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. (c) 2018 American Institute of Chemical Engineers AIChE J, 65: 702-711, 2019