Separation of piperidine-2,6-dione drug enantiomers by micellar electrokinetic capillary chromatography using synthetic chiral surfactants

The enantioselective separation of five racemic piperidine-2,6-dione compounds was accomplished using chiral micelle electrokinetic capillary chromatography. This class of drugs includes glutethimide, aminoglutethimide, cyclohexylaminoglutethimide, pyridoglutethimide, and phenglutarimide. The resolution of all five compounds with simultaneous enantioselective separation of four of the five was obtained in a single run, using the synthetic chiral surfactant (S)-N-dodecoxycarbonylvaline. An enantioselective separation of the fifth compound was obtained by a second synthetic chiral surfactant, (R)-dodecoxycarbonylproline. It was observed that surfactant type and concentration, pH, and sample matrix all effect enantiomeric resolution. The migration order of cyclohexylaminoglutethimide enantiomers was confirmed by injecting a sample comprised mostly of the (-)-enantiomer. In addition, the separation of a sixth related sample (a thalidomide mixture) is shown to be achiral and not enantiomeric, as verified by the lack of enantiomer migration order reversal.