Mechanistic study on the opposite migration order of the enantiomers of ketamine with α- and β-cyclodextrin in capillary electrophoresis

The enantiomer migration order of the chiral anaesthetic drug ketamine [RS-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone] was studied by capillary electrophoresis using various cyclodextrins as chiral selectors. The opposite migration order of the enantiomers of ketamine was observed when native α- and β-cyclodextrins were used as chiral selectors in capillary electrophoresis. The possible mechanisms of the opposite enantiomer migration order were investigated by employing electrospray ionization mass spectrometry, 1H-NMR spectrometry, one dimensional rotating frame nuclear Overhauser and exchange spectroscopy, X-ray crystallography, and molecular modeling techniques. As this study indicates, capillary electrophoresis can be used as a reliable experimental technique for examination of the correctness of the results of molecular modeling calculations. In addition, based on X-ray crystallographic analysis it was confirmed that (–)-ketamine as a free base possesses S configuration.