Comparison of chromatographic techniques for diastereomer separation of a diverse set of drug-like compounds

Preparative supercritical fluid chromatography (SFC) has proven value for isocratic bulk separation of both diastereomers and enantiomers. With the recent availability of SFC equipment suitable for rapid gradient separation [Ebinger et al. JALA (2011) 16 (3) 241], we have become interested in comparing the effectiveness of traditional reverse phase high performance liquid chromatography (HPLC) with SFC using non-chiral columns for the separation of diastereomeric mixtures. The success rates for separation of a diverse set of 258 synthetic diastereomer pairs were used to determine the relative utility of the aforementioned two techniques. Our results suggest that gradient non-chiral SFC was more successful than the traditional non-chiral HPLC technique for diastereomer separations of the diverse sample set of 258 drug-like compounds.

► Gradient HPLC and SFC were compared for diastereomer separation on achiral columns. ► SFC provided higher success rates than HPLC for diastereomer separation. ► Unmodified silica and 2-pyrenyl-ethyl bonded silica performed best by SFC.