Enantioseparation of flobufen with cyclodextrins studied by capillary electrophoresis and NMR.
OBJECTIVE
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 complexation 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)-beta-cyclodextrin (TM-beta-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-beta-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.
Lambert
A
A
Laboratoire de Chimie Analytique, Faculté de Pharmacie, Nancy, France.
Ballon
J M
JM
Nicolas
A
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002087:Butyrates / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002087:Butyrates; D003505:Cyclodextrins; C056474:flobufen