The effect of high concentration additive on chiral separations in supercritical fluid chromatography

•Highest enantioselectivity for the separations of primary amines with 10% of isopropylamine as additive.•The concentration of isopropylamine impacted mostly the retention of one enantiomer.•The ratio isopropylamine/ethanol determines enantioselectivity.•Chiralpak AD-3 remained stable using 10% of isopropylamine dissolved in the modifier.

Supercritical Fluid Chromatography is frequently used to efficiently handle separations of enantiomers. The separation of basic analytes usually requires the addition of a basic additive in the mobile phase to improve the peak shape or even to elute the compounds. The effect of increasing the concentration of 2-propylamine as additive on the elution of a series of basic compounds on a Chiralpak-AD stationary phase was studied. In this study, unusual additive concentrations ranging from 0.3% to 10% of 2-propylamine 2-propylaminein the modifier were explored and the effect on retention, peak shape, selectivity and resolution was evaluated. The addition of a large quantity of additive allowed to drastically improve the selectivity and the resolution, and even enantiomers elution order reversal was observed by changing the concentration of basic additive. The role of the ratio additive/modifier appeared a key to tune the enantioselectivity. Finally, the impact of these drastic conditions on the column material was evaluated.