A priori selection of the mobile and stationary phase in centrifugal partition chromatography and counter-current chromatography

The selection of the mobile and the stationary phase in support-free liquid–liquid chromatography (centrifugal partition chromatography and counter-current chromatography) is equivalent to a selection of a biphasic liquid system and its global composition. There is an immense number of choices of biphasic liquid systems. On one hand what makes this technique extremely versatile, on the other hand turns the selection of the appropriate system for a particular separation problem into a challenging and demanding task. In this work a systematic procedure for the selection of biphasic liquid systems for preparative scale separations is presented. The procedure is adaptable to the production scale requirements including production cost and safety. The experimental effort of different stages of the selection procedure is minimized by using a fully predictive method, the conductor-like screening model for real solvents (COSMO-RS). The COSMO-RS is used to assess properties relevant for the selection of a biphasic liquid system, such as the solute solubility and the partition coefficient.

► A systematic procedure for the selection of biphasic solvent systems in support-free liquid–liquid chromatography is presented.
► The procedure meets the requirements of preparative scale separations, related to cost and safety issues.
► A fully predictive thermodynamic method, COSMO-RS, is used to estimate the solute solubility and partition coefficient.
► The time, resources, and overall cost of the selection of mobile and stationary phase is reduced.
► The proposed method was tested using model target solutes.