Enantiomeric separation of some piperidine-2,6-dione drugs on tolylcellulose by liquid chromatography

The direct liquid Chromatographic resolution of a group of drugs, all having a piperidine-2,6-dione structure in common was investigated using a cellulose-based chiral stationary phase. The experimental tris(4-methylbenzoate) cellulose column (Bio-Rad RSL, Belgium) has the polymeric layer covalently bonded onto an aminopropylated silica support. Reversed phase as well as normal phase conditions were applied without deterioration of the column. Aminoglutethimide and glutethimide were easily resolved using methanol-water mixtures as mobile phase. Acetylaminoglutethimide, the major metabolite of aminoglutethimide, was separated from the parent drug but its enantiomers were not completely resolved. Thalidomide enantiomers were at best resolved under normal phase conditions with n-hexane as the major constituent of the mobile phase. No chiral interaction on this column was noticed for 3-phenylacetylaminopiperidine-2,6-dione.