The first systematic study of liquid-liquid chromatography (LLC) in the nonlinear range of the distribution isotherm.

Pulse injection experiments with cannabidiol (CBD, 1–300 mg/mL) were performed in three units of different designs and volumes (20 mL-2 L).

At higher concentrations, the CBD elution profiles showed a diffusive front and sharp rear part.

The elution profiles were successfully simulated with the equilibrium-cell model and a nonlinear correlation describing the CBD distribution isotherm.

The distribution isotherm parameters were determined by the peak fitting method.

Liquid-liquid chromatography (LLC) is a technique in which the separation of mixture components is achieved due to their different distribution between the two phases of a pre-equilibrated biphasic solvent system. In this work, the LLC operation in the nonlinear range of the distribution isotherm was systematically examined for the first time. The influence of the feed concentration on the elution profiles of a model component (cannabidiol, CBD) was studied in three LLC units of different types and sizes ranging from ∼20 mL to ∼2 L. A series of pulse injections with CBD concentrations varying from 1 to 300 mg/mL was performed with n-hexane/methanol/water 5/4/1 (v/v/v) in descending mode (lower phase as the mobile phase). The elution profiles were simulated using the equilibrium-cell model and an anti-Langmuir-like equation for describing the CBD distribution equilibria. The distribution equilibria equation parameters were fitted to the CBD elution profiles using the peak fitting method. The model was validated and provided good predictions of the CBD elution profiles in the entire concentration range for all three LLC units.

Countercurrent chromatography

Centrifugal partition chromatography

Nonlinear distribution equilibria

Mathematical modeling

Cannabidiol (CBD)

Data will be made available on request.

© 2023 Elsevier B.V. All rights reserved.