Fine optimization of twin-column recycling chromatography with a solvent gradient for the removal of minor impurities

摘要

In the present study, during removal of minor impurities by twin-column recycling chromatography with a solvent gradient, a compressing band effect was generated to offset band spreading and retain the principal component band within one column. For real-time monitoring, a detector was mounted on-line after the upstream column to monitor when the tail of the principal component was eluted from this column. When the conditions fluctuated, the column were switched to ensure successful separation without the need to determine the adsorption equilibrium in advance. Optimization of the operating conditions revealed that increasing the solvent gradient improved pre-impurity separation but impeded post-impurity removal. Changing the feed volume within a certain range hardly affected separation of the impurities, and increasing the number of cycles enhanced separation of the impurities. (C) 2019 Elsevier B.V. All rights