Nicotine in tobacco product aerosols: 'It's déjà vu all over again'.

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 () 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: = 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 ≈ 1. At cigarette-like total nicotine concentration (Nic) values of ~60 mg/mL, e-liquid aerosol droplets with ≈ 1 are harsh upon inhalation. The design evolution for e-liquids has paralleled that for smoked tobacco, giving a 'déjà vu' trajectory for . For 17th-century 'air-cured' tobacco, in the smoke particles was likely ≥ 0.5. The product Nic 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 ≈ 0.02 and lowered harshness. Some tobacco cigarette formulations/designs have been adjusted to restore some nicotine sensory 'kick/impact' with ≈ 0.1, as for Marlboro. Overall, for tobacco smoke, the de-freebasing trajectory was ≥ 0.5 → ~0 →~0.1, as compared with = ~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.