High Variability in Nicotine Analog Contents, Misleading Labeling, and Artificial Sweetener in New E-Cigarette Products Marketed as "FDA-Exempt"

The recent introduction of electronic cigarette products containing a synthetic nicotine analog, 6-methyl nicotine, challenges the tobacco regulatory authority of the United States Food and Drug Administration (FDA). A similar strategy is pursued by vendors of recently introduced e-cigarette liquids containing nicotinamide, marketed as Nixotine or Nixamide. Compared to nicotine, 6-methyl nicotine is pharmacologically more potent at nicotinic receptors, and more toxic, raising concerns about increased addictiveness and adverse effects. Here, combinations of gas chromatography, high performance liquid chromatography and mass spectrometry were used to determine nicotine analogs, flavor and sweetener contents of e-cigarette liquids of the brands SpreeBar and Nixotine products. All SpreeBar products, labelled as containing 5% 6-methyl nicotine, contained only 0.61-0.64% 6 methylnicotine, while Nixotine samples contained 7-46% less of the declared nicotinamide contents. Although Nixotine product labels did not list 6MN as an ingredient, small amounts of 6-methyl nicotine were detected. All SpreeBar samples contained the artificial sweetener neotame (0.20-0.86μg/mg). Results identified significant discrepancies between declared and measured constituents of e-cigarette products containing nicotine alternatives. The discrepancy is misleading for consumers and raises concerns about production errors. SpreeBar products also contained neotame, a high-intensity sweetener with high heat stability, likely increasing appeal to young and first-time users. Novel e-cigarette products with misleading labels containing nicotine analogs instead of nicotine on the US market is concerning and should be urgently addressed by lawmakers and regulators. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by cooperative agreement U54DA036151 (Yale Tobacco Center of Regulatory Science) from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) and the Center for Tobacco Products of the US Food and Drug Administration (FDA). The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors