Updating a generic screening approach in sub- or supercritical fluid chromatography for the enantioresolution of pharmaceuticals

• Investigation of 2-propanol-containing mobile phases in SFC.
• Use of polysaccharide-based stationary phases.
• Evaluation of the enantioselectivity and complementarity with methanol-containing mobile phases.
• Principal component analysis of the data.
• Definition of a chiral screening step.

This work focusses on the update of a generic chiral screening approach in sub- or supercritical fluid chromatography (SFC). Newly generated data with 2-propanol-containing mobile phases on 12 polysaccharide-based stationary phases was combined with previous data obtained using methanol-containing mobile phases. As modifiers 2-propanol and methanol were selected for their earlier performance. An evaluation of the most appropriate solvent strength is made and the enantioselective behaviour of the chromatographic systems is discussed. A comparison of the systems is made and their complementarity investigated by analyzing the data by different means, e.g. principal component analysis. The generic screening sequence is proposed by selecting the most enantioselective and complementary systems. This allows updating an existing screening strategy. With the novel screening, all compounds of a 57-compounds test set were separated (48 baseline), on at least one of four selected systems, within an analysis time of 30 min. The applicability and performance of the updated screening was demonstrated with a compound from the test set, i.e. alprenolol.

Scheme of (a) the initial screening step as defined by Maftouh et al. [14] and (b) the updated version of the screening step. In the top row the CSPs are presented while the second row represent the used modifier in the carbon-dioxide based mobile phases.Figure optionsDownload as PowerPoint slide