Enantiomeric separation of zopiclone, its metabolites and products of degradation on a ß-cyclodextrin bonded phase

Abstract

In this paper the separation of zopiclone (ZP) enantiomers, its degradation products and chiral metabolites, has been investigated on a ß-cyclodextrin bonded phase. The liquid chromatographic behavior of the enantiomers of zopiclone, zopiclone-N-oxide (OXZP) and N-desmethyl-zopiclone (DMZP) has been studied with respect to mobile-phase composition, pH, ionic strength and the nature of the organic modifier. Based on the results, conditions were chosen for the separation of the enantiomers of zopiclone, its chiral metabolites and its related degradation products. The separation selectivity of a ß-cyclodextrin (ß-CD) bonded-phase column was examined. Further, based on crystallographic data, a computer model of the ZP molecule has been designed by using the HyperChem program in order to estimate the possibility of the different groups to interact with the ß-CD and to give a plausible explanation of the mechanism of chiral discrimination.