Fraction of free-base nicotine in fresh smoke particulate matter from the eclipse "cigarette" by ¹H NMR spectroscopy

Solution ¹H NMR (proton-NMR) spectroscopy was used to measure the distribution of nicotine between its free-base and protonated forms at 20 °C in (a) water; (b) glycerin/water mixtures; and (c) puff-averaged "smoke" particulate matter (PM) produced by the Eclipse cigarette, a so-called "harm reduction" cigarette manufactured by R. J. Reynolds (RJR) Tobacco Co. Smoke PM from the Eclipse contains glycerin, water, nicotine, and numerous other components. Smoke PM from the Eclipse yielded a signal for the three N-methyl protons on nicotine at a chemical shift of δ (ppm) = 2.79 relative to a trimethylsilane standard. With α_fb = fraction of the total liquid nicotine in free-base form, and α_a = fraction in the acidic, monoprotonated NicH⁺ form, then α_a + α_fb ≈ 1. (The diprotonated form of nicotine was assumed negligible.) When the three types of solutions were adjusted so that α_a ≈ 1, the N-methyl protons yielded δ_a = 2.82 (Eclipse smoke PM); 2.79 (35% water/65% glycerin); and 2.74 (water). When the solutions were adjusted so that α_fb 1, the N-methyl protons yielded δ_fb = 2.16 (Eclipse smoke PM); 2.13 (35% water/65% glycerin); and 2.10 (water). In all of the solutions, the rate of proton exchange between NicH⁺ and Nic was fast relative to the 1H-NMR chemical shift difference in hertz. Each solution containing both NicH⁺ and Nic thus yielded a single N-methyl peak at a δ given by δ = α_aδ_a + α_fbδ_fb so that δ varied linearly between δ_a and δ_fb. Since α_fb = (δ_a - δ)/(δ_a - δ_fb), then δ = 2.79 for the unadjusted Eclipse smoke PM indicates α_fb ≈ 0.04. The effective pH of the Eclipse smoke PM at 20 °C may then be calculated as pH_eff = 8.06 + log[α_fb/(1 - α_fb)] = 6.69, where 8.06 is the pK_a of NicH⁺ in water at 20 °C. The measurements obtained for the puff-averaged Eclipse smoke PM pertain to the chemistry of the smoke PM as it might be initially inhaled at 20 °C. Upon inhalation, the volatilization of nicotine and other acid/base active compounds (as well as a warming toward a body temperature of 37 °C) will alter the pH_eff value of the smoke PM during the time that it resides and ages in the respiratory tract.