DETERMINATION OF ENANTIOMERIC PURITY OF NICOTINE IN PHARMACEUTICAL PREPARATIONS BY C-13-NMR IN THE PRESENCE OF A CHIRAL LANTHANIDE SHIFT-REAGENT

A method for the determination of enantiomeric composition of nicotine samples, based on C-13-NMR spectroscopy in the presence of the chiral lanthanide shift reagent, tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]ytterbium [Yb(tfc)3], was developed. Observation at 100.6 MHz of the C2' resonance of nicotine in the presence of 0.15-0.20 mol of the ytterbium complex, either in ordinary C-13{H-1}-NMR spectra or in carbon spectra enhanced by polarization transfer (refocused INEPT), allowed precise determination of the ratios of (S)- to (R)-nicotine. At least 1% of (R)-nicotine could be determined in samples of (S)-nicotine, milligram amounts being required for the analysis. Use of the C-13-NMR spectra is more advantageous than use of H-1-NMR spectra. Thus, Yb(tfc)3 induced separation of the proton resonances of the enantiomers of nicotine, and the shifted resonances of nicotine enantiomers could be assigned by use of H-1-C-13 heteronuclear chemical shift correlation, but the proton resonances were broad, their chemical shifts were sensitive to small variations of the ratio between Yb(tfc)3 and nicotine, and signals of the enantiomer present in small amounts were easily obscured by impurities. Therefore, although C-13-NMR is more time consuming, this method is more suitable for routine analysis. The method was applied for the determination of enantiomeric purity of (S)-nicotine in pharmaceutical formulations, including chewing gums, skin absorption patches, inhalators, and nasal sprays.