Free-Base Nicotine Determination in Electronic Cigarette Liquids by ¹H NMR Spectroscopy

High Resolution Image Download MS PowerPoint Slide E-liquids usually contain significant nicotine, which will exist primarily in two forms, monoprotonated and free-base, the proportions of which are alterable through the effective pH of the medium. The fraction of nicotine in the free-base form is α fb, with 0 ≤ α fb ≤ 1. When dosed via aerosol, the two nicotine forms have different mechanisms and kinetics of delivery, as well as differing implications for harshness of the inhaled aerosol, so α fb is relevant regarding abuse liability. Previous attempts to determine α fb in electronic cigarette liquids and vapor have been flawed. We employed the exchange-averaged 1 H NMR chemical shifts of nicotine to determine α fb in samples of e-liquids. This method is rapid and direct and can also be used with collected aerosol material. The e-liquids tested were found to have 0.03 ≤ α fb ≤ 0.84. The α fb values in collected aerosol liquid samples were highly correlated with those for the parent e-liquids. E-liquids designed to combine high total nicotine level (addictive delivery) with low α fb (for ease of inhalation) are likely to be particularly problematic for public health.