DETERMINATION OF FLUOXETINE HYDROCHLORIDE ENANTIOMERIC EXCESS USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH CHIRAL STATIONARY PHASES

Chromatographic methods using chiral stationary phases have been devel oped for the separation of fluoxetine hydrochloride enantiomers. Ovomu coid and tris(3,5-dimethylphenyl carbamate) cellulose stationary phase s were used in the reversed- and normal-phase modes, respectively. Acc eptable isomer separation was achieved at pH 3.5 with the ovomucoid ph ase, but peak shapes were broad and the separation was quite sensitive to the acetonitrile concentration in the mobile phase. Isopropyl alco hol and methyl-tert-butyl ether mobile phase modifiers each provided c omplete resolution using the derivatized cellulose column. Better sepa ration robustness was obtained with a column temperature of 1 degrees C using the isopropyl alcohol modifier. The methyl-tert-butyl ether sy stem was robust at room temperature. Differences in relative enantiome r amounts of as little as 2% could be determined. The chromatographic conditions provided a much more discriminating test compared to an opt ical rotation method proposed for pharmacopeial use which had difficul ty distinguishing individual enantiomers. The chiral chromatographic c onditions were also applied to capsule formulations to demonstrate the presence of racemic fluoxetine hydrochloride. (C) 1998 Elsevier Scien ce B.V. All rights reserved.