Chiral selectors for enantioresolution and quantitation of the antidepressant drug fluoxetine in pharmaceutical formulations by (19)F NMR spectroscopic method.

(19)F NMR spectroscopy was applied to the quantitative determination of fluoxetine enantiomers using different chiral recognition agents in pharmaceutical formulations. Several parameters affecting the enantioresolution including the type and concentration of chiral selector, concentration of fluoxetine and temperature were studied. The chiral selectors investigated are the cyclic oligosaccharides alpha-, beta- and gamma-cyclodextrin and a diamino derivative of methylated alpha-cyclodextrin (DAM-alpha-CD), linear polysaccharides (maltodextrin with dextrose equivalents of 4.0-7.0, 13.0-17.0 and 16.5-19.5) and the macrocyclic antibiotic vancomycin. Among the chiral selectors used, DAM-alpha-CD turned out to give the best resolution of the (19)F NMR signals of (R)- and (S)-fluoxetine. The calibration curve was linear for (R)- and (S)-fluoxetine over the range 0.10-1.35 mgmL(-1), the detection limits (S/N=3) being 5.9 and 7.5 microgmL(-1) for the pure solutions of (R)- and (S)-fluoxetine, respectively. The recovery studies performed on pharmaceutical samples ranged from about 90 to 110% with relative standard deviations of <8%. The results showed that the proposed method is rapid, precise and accurate. Applying statistical Student's t-test revealed insignificant difference between the real and measured contents at the 95% confidence level.