Purpose . The aim of this study was to obtain the resolution of flobufen enantiomers, an antiinflammatory active substance, by capillary electrophoresis with cyclodextrins. The mechanism of com- plexation and determination of the stoichiometry of the complexes were studied by NMR and the analytical method was developed and validated.
Methods . Zone capillary electrophoresis coupled to direct ultraviolet detection was selected. The interaction between flobufen and the chiral selector was studied by NMR. Optimization of the separation was performed using a Box-Wilson Central Composite Design for three factors related to the composition of the electrolyte.
Results . Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) was found to be the most efficient selector via the formation of a 1:1 complex proved by NMR. Constants of complexation of flobufen enantiomers were determined by NMR and capillary electrophoresis. Optimal values for the critical factors of the analytical system were: pH (5.50), content in methanol (10% v/v), and TM-β-CD (30 mM). The ability of capillary electrophoresis to quantify as low as 0.1% (w/w) of R in S-flobufen or vice-versa was established.
Conclusions . Capillary electrophoresis was shown to be a valuable method to control the enantiocomposition of flobufen by use of a chiral selector whose interactions with the analytes could be explored by NMR.