Purification and Concentration of Minor Impurity in the Bulk Drug by Step-Gradient Twin-Column Recycling Chromatography

Abstract

A weaker solvent was constantly added at the middle of the two columns to set up a two-step solvent gradient in twin-column recycling chromatography so that the eluotropic strength of the downstream liquid was reduced. Therefore, the back edge of the band moved faster than the front edge during the circulation of the solute band, initiating special gradient compression to effectively counteract the band spreading. Herein, modified recycling chromatography was applied to the simultaneous purification and concentration of minor impurities in the bulk drug. Taking orlistat as an example, the target impurity with only 0.7% content in orlistat bulk drug was isolated, giving a purity of 96%. Its concentration was enhanced by 9.4 times. Investigations on operating conditions verified that decreasing the eluent eluotropic strength, increasing the solvent gradient, extending the column switching interval, and enhancing the number of switches within proper ranges were beneficial to the improvement of separation.

Improvement of oligonucleotide separation using a repetto high‐performance liquid chromatography recycling approach

“…As an alternative, a so-called twin-column approach was later developed for analytical HPLC in which separation is carried out by flipping analytes between two columns without a need for passage through the pump [26]. This approach has gained popularity with several alternative applications described in the literature [27][28][29][30]. Aside from a need for a second column, however, this approach doubles the back pressure, which may pose a problem for the columns as well as a detector placed inside the high-pressure recycling loop.…”

Enhanced Purification of 7-Xylosyl-10-deacetyl Paclitaxel through Twin-Column Recycling Chromatography with a Step Solvent Gradient

“…In practice, however, the expected separation of recycling chromatography is difficult to achieve due to band broadening, caused by various factors such as axial dispersion, slow mass transfer, and nonlinear adsorption . In our previous study, it was found that solvent gradient could generate a mechanism to suppress broadening, , and by introduction of a modifier between the two columns, the eluotropic strength of the downstream liquid was reduced, resulting in a slower movement of the band front in comparison to the tail. Hence, a band compression was stimulated to counteract band spreading. , …”