Solvent System Selection Strategies in Countercurrent Separation

Abstract

The majority of applications in countercurrent and centrifugal partition chromatography, collectively known as countercurrent separation, are dedicated to medicinal plant and natural product research. In countercurrent separation, the selection of the appropriate solvent system is of utmost importance as it is the equivalent to the simultaneous choice of column and eluent in liquid chromatography. However, solvent system selection is often laborious, involving extensive partition and/or analytical trials. Therefore, simplified solvent system selection strategies that predict the partition coefficients and, thus, analyte behavior are in high demand and may advance both the science of countercurrent separation and its applications. The last decade of solvent system selection theory and applications are critically reviewed, and strategies are classified according to their data input requirements. This offers the practitioner an up-to-date overview of rationales and methods for choosing an efficient solvent system, provides a perspective regarding their accuracy, reliability, and practicality, and discusses the possibility of combining multiple methods for enhanced prediction power.

Sweet spot matching: A thin-layer chromatography-based countercurrent solvent system selection strategy

“…Hexanes-ethyl acetate-methanol-water (HEMWat), chloroform-methanol-water (ChMWat), and ethyl acetate- n -butanol-water (EBuWat) SS families were studied [3]. These three SS families were used initially along with 29 commercially available natural products to validate the proposed R f sweet spot in the “normal prediction” strategy.…”

“…It can be divided into hydrodynamic mode, i.e., countercurrent chromatography, and hydrostatic mode, i.e., centrifugal partition chromatography [1]. Because of the consistency of the partition coefficient (K value), the solvent system compatibility, and the reproducibility of column behavior, centrifugal CCS provides orthogonal and scalable separation capabilities [3]. Thus, it has been widely used for natural product research [4–11].…”

“…Usually, it involves many partitioning experiments to screen for a SS that yields the appropriate K value(s) to deliver the target analyte(s) into the K value sweet spot of optimum resolution, which has been defined as 0.4 < K < 2.5 in regular elution mode [13,14]. To minimize the tedious bench work required for SS selection, a series of biphasic SS selection strategies have been developed [3]. Among these, in 1979, Hostettmann et al recommended a TLC-based SS selection strategy as the first step towards providing the CCS practitioner with a more rapid assessment of various SS formulations.…”

Countercurrent assisted quantitative recovery of metabolites from plant-associated natural deep eutectic solvents

“…This technology is orthogonal to solid phase-based LC, can avoid sample loss resulting from degradation or absorption on a solid support, and thus, is characterized by high recovery and reproducibility [9,10]. At the same time, as the stationary phase in CCS is a liquid, its separation and resolution essentially depend on the partition coefficient ( K ) value of each analyte, representing their relative distribution between the stationary and mobile phases of a given solvent system [11].…”

The Generally Useful Estimate of Solvent Systems (GUESS) method enables the rapid purification of methylpyridoxine regioisomers by countercurrent chromatography

“…CCC, CPC and related technologies have been used for the isolation of natural products [2], separation of isomers [3], and purification of organic synthetic products [4]. An appropriate solvent system is the key for high resolution in CCC and CPC separations [5]. The solvent system selection procedure is, however, multistep and time-consuming [6].…”