Qualitative and Quantitative Analyses of the Enantiomers of Nicotine and Related Alkaloids Employing Chiral Supercritical Fluid Chromatography in Commercial Nicotine Samples and in E-Cigarette Products

Abstract

Summary Several commercial sources of tobacco-derived nicotine (TDN) and synthetic nicotine (SyN) and a variety of e-cigarette liquids employing either TDN or SyN have been evaluated to determine the enantiomer distributions of R- and S-nicotine and R- and S-nornicotine by chiral supercritical fluid chromatography (chiral-SFC) with UV diode array detection (DAD-UV). The data generated are used to test the mismatched vs. matched hypothesis of Cheetham et al. as a means to distinguish products containing TDN from products with SyN. Two sets of experiments were conducted in this study. The first experiment was conducted on a series of 11 commercial nicotine samples (three characterized as tobacco-derived and eight characterized as synthetic nicotine). The commercial nicotine samples were either from a tobacco-derived nicotine (TDN) source or were synthetic nicotine (SyN). Some of the commercial nicotine samples were nicotine salts. The second experiment was conducted on e-liquids from a set of 11 e-cigarettes. The nicotine in the e-liquids was either from TDN or SyN. The e-liquid samples were differentiated based on the advertised information on the internet or from printed information on the e-cigarette packaging. None of the three commercial TDN samples in the first experiment could be unequivocally characterized as coming from a tobacco source. Five of the eight commercial SyN samples were correctly characterized as SyN based on the matched vs. mismatched nicotine and nornicotine hypothesis of Cheetham et al. In the second experiment, none of the e-liquids characterized as being from TDN sources could be unequivocally characterized as coming from a tobacco source. All of the e-liquids characterized as being from SyN sources were either characterized as equivocal or of uncertain origin based on the matched vs. mismatched nicotine and nornicotine hypothesis of Cheetham et al. These sets of experiments represent an excellent example of the difficulty that the United States Food and Drug Administration is having in trying to determine if TDN or SyN is being used in tobacco products. Even highly advanced chromatographic methods such as chiral-SFC were not able to unequivocally distinguish products with TDN from products with SyN 100% of the time. Other analytical methods such as 14C quantitation of nicotine samples by accelerator mass spectrometry offer a more reliable determinate of nicotine source (TDN vs. SyN) and can be used to identify misbranded products labelled as containing SyN, even though this methodology is more expensive and offered in limited locations.