Supercritical fluid chromatography for milligram preparation of enantiomers

Preparative chromatographic enantioseparation is now the preferred technique for obtaining milligram quantities of pure enantiomers in the initial phase of development of a therapeutic compound. Supercritical fluid chromatography offers several advantages over liquid chromatography and was therefore selected for the preparative enantioseparation of a new potential anti-inflammatory molecule. Approximately 10 mg of each of the two enantiomers was successfully prepared using a Chiralpak AD-H (tris-3,5-dimethylphenylcarbamate of amylose) polysaccharide-based stationary phase with 40% of ethanol as a co-solvent, using a stacked injection mode. A peak distortion was observed during volume overloading, which may be due to the mixed-stream injection method.