Chiral Separation of Fluoxetine and Its Analogs with Charged Cyclodextrins by Capillary Electrophoresis

Abstract

Chiral separation of fluoxetine was performed by capillary electrophoresis (CE) using 11 different cyclodextrins (CDs) including neutral and charged derivatives as chiral selectors. The separation conditions were optimized in terms of the type of the CDs and their concentration, as well as pH of the background electrolyte. The optimized conditions offered usefulness in determination of a trace amount of chiral impurity with a limit of quantitation (LOD) of 0.2% and a limit of detection (LOD) of less than 0.1%. Four fluoxetine analogs that have different substituents on the amine moiety were also analyzed by CE to study the structural effects on chiral recognition. Three of them that have simple alkyl substituents showed similar separation behavior to that of fluoxetine, while addition of a carboxyl group on the amine moiety caused a significant change in chiral separation. The charge on both the analytes and the CDs was found to be one of the important factors, which affected chiral separation.

Keywords:

• Chiral separation
• Capillary electrophoresis
• Cyclodextrins
• Fluoxetine

Acknowledgments

Mr. Lawrence C. Creemer (Eli Lilly and Company) is thanked for valuable discussion and suggestion. The advice and support from Drs. Mark R. Glick, Herbert A. Kirst, Robin S. Readnour, and Bernard A. Olsen (Eli Lilly and Company) are gratefully acknowledged.