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Investigation on the enantioseparation of duloxetine by capillary electrophoresis, NMR, and mass spectrometry

Abstract:

The enantiomeric separation of the antidepressant drug duloxetine was investigated by CE using 15 neutral CDs as chiral selectors. Among them, (2-hydroxypropyl)-β-CD and methyl-γ-CD gave rise to the highest enantioresolution. The enantiomer migration order for duloxetine was found to be reversed depending on the CD employed: R-duloxetine was the first-migrating enantiomer for (2-hydroxypropyl)-β-CD while it was the secondmigrating enantiomer for methyl-γ-CD. NMR and MS experiments were performed in order to justify this behavior. Although the elucidation of the structure of the enantiomer-CD complexes was not possible, their averaged stoichiometry was studied and their apparent and averaged equilibrium constants were calculated. The results obtained showed that the chiral separation of duloxetine by CE depends not only on the thermodynamic stability of the enantiomer-chiral selector complexes but also on their electrophoretic mobility.