Enantioselectivity of polysaccharide-based chiral stationary phases in supercritical fluid chromatography using methanol-containing carbon dioxide mobile phases

The enantioselectivity of twelve chiral stationary phases (CSPs) and four methanol-containing carbon dioxide mobile phases (MPs) is evaluated in supercritical fluid chromatography (SFC) with a test set of 59 chiral pharmaceutical compounds. Methanol (MeOH) is evaluated as modifier in carbon dioxide (CO2) since it is commonly used in chiral SFC because of its favorable characteristics and proven successes. In addition to the MP of earlier defined generic screening conditions, new MPs, which contained both a basic (isopropylamine) and an acidic (trifluoroacetic acid) additive, were investigated and yielded broad enantioselectivities. The joint use of the additives impacts the enantioselectivity differently than the individual. Polysaccharide-based CSPs from different manufacturers were assessed, which showed that CSPs containing the same selector do not always display the same enantioselectivity. This work enabled not only to identify the individual chiral systems with the broadest enantioselectivity but also to determine their complementarity, resulting in a limited set of systems with the broadest enantioselectivity. As a result an updated, fast and efficient screening sequence was proposed.

► Investigation of 4 methanol-containing carbon dioxide mobile phases in SFC. ► Use of 12 polysaccharide-based stationary phases. ► Separate and joint use of IPA and TFA. ► Evaluation of the enantioselectivity and complementarity. ► Definition of a screening sequence with 3 systems and 94.9% success rate.