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

Abstract

The recent introduction of electronic cigarette products containing a synthetic nicotine analog, 6-methyl nicotine (6MN), challenges FDA's tobacco regulatory authority. A similar strategy is pursued by vendors of recently introduced e-cigarette liquids containing nicotinamide (NA), marketed as 'Nixotine' or 'Nixamide'. Compared to nicotine, 6MN 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 ECBlend "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.

FIGURE

(A) 6-methyl nicotine and nicotinamide; the red star indicates the chiral center (B) Photo of side of cardboard packaging of 2 different ‘SpreeBar’ flavor pods, labelled “5%”, stating “Contains proprietary Metatine”, which is the trademark name for 6-methyl nicotine (bottom right); (C) Front and back of ‘Nixotine’ refill bottle, indicating only the presence of nicotinamide but not 6-methyl nicotine; indication of other ingredients (“Kosher USP Propylene Glycol (PG), Kosher USP Palm Vegetable Glycerin (VG), Natural and Artificial flavors”); and warning only about nicotinamide.