Chiral stationary phase optimized selectivity liquid chromatography: A strategy for the separation of chiral isomers

•Stationary phase Optimized Selectivity LC was applied to chiral separations.•Predictions of retention time were achievable with good accuracies.•Baseline separation could be achieved in both isocratic and gradient modes.

Chiral Stationary-Phase Optimized Selectivity Liquid Chromatography (SOSLC) is proposed as a tool to optimally separate mixtures of enantiomers on a set of commercially available coupled chiral columns. This approach allows for the prediction of the separation profiles on any possible combination of the chiral stationary phases based on a limited number of preliminary analyses, followed by automated selection of the optimal column combination. Both the isocratic and gradient SOSLC approach were implemented for prediction of the retention times for a mixture of 4 chiral pairs on all possible combinations of the 5 commercial chiral columns. Predictions in isocratic and gradient mode were performed with a commercially available and with an in-house developed Microsoft visual basic algorithm, respectively. Optimal predictions in the isocratic mode required the coupling of 4 columns whereby relative deviations between the predicted and experimental retention times ranged between 2 and 7%. Gradient predictions led to the coupling of 3 chiral columns allowing baseline separation of all solutes, whereby differences between predictions and experiments ranged between 0 and 12%. The methodology is a novel tool allowing optimizing the separation of mixtures of optical isomers.