Introduction The distribution of nicotine among its free-base (fb) and protonated forms in aerosolised nicotine affects inhalability. It has been manipulated in tobacco smoke and now in electronic cigarettes by the use of acids to de-freebase nicotine and form ‘nicotine salts’.
Methods Measurements on electronic cigarette fluids (e-liquids) were carried out to determine (1) the fraction of nicotine in the free-base form (αfb) and (2) the levels of organic acid(s) and nicotine. Samples included JUUL ‘pods’, ‘look-a-like/knock-off’ pods and some bottled ‘nicotine salt’ and ‘non-salt’ e-liquids.
Results αfb= 0.12 ±0.01 at 40°C (≈ 37°C) for 10 JUUL products, which contain benzoic acid; nicotine protonation is extensive but incomplete.
Discussion First-generation e-liquids have αfb ≈ 1. At cigarette-like total nicotine concentration (Nictot) values of ~60 mg/mL, e-liquid aerosol droplets with αfb≈ 1 are harsh upon inhalation. The design evolution for e-liquids has paralleled that for smoked tobacco, giving a ‘déjà vu’ trajectory for αfb. For 17th-century ‘air-cured’ tobacco, αfb in the smoke particles was likely ≥ 0.5. The product αfbNictot in the smoke particles was high. ‘Flue-curing’ retains higher levels of leaf sugars, which are precursors for organic acids in tobacco smoke, resulting in αfb ≈ 0.02 and lowered harshness. Some tobacco cigarette formulations/designs have been adjusted to restore some nicotine sensory ‘kick/impact’ with αfb≈ 0.1, as for Marlboro. Overall, for tobacco smoke, the de-freebasing trajectory was αfb ≥ 0.5 → ~0 →~0.1, as compared with αfb= ~1 →~0.1 for e-cigarettes. For JUUL, the result has been, perhaps, an optimised, flavoured nicotine delivery system. The design evolution for e-cigarettes has made them more effective as substitutes to get smokers off combustibles. However, this evolution has likely made e-cigarette products vastly more addictive for never-smokers.
- electronic nicotine delivery devices
- tobacco industry
- harm reduction
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Contributors AKD carried out the experimental work; JFP conceived the work; and DHP directed the work. All authors contributed to the writing of the manuscript.
Funding This work was supported by the US National Institutes of Health (grant R01ES025257). Research reported was supported by the National Institute of Environmental Health Sciences and the Food and Drug Administration Center for Tobacco Products.
Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the FDA.
The quote in the title has been attributed to Yogi Berra.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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