Free-Base and Protonated Nicotine in Electronic Cigarette Liquids and Aerosols

Abstract

Introduction Reliable characterization of the nicotine content and emissions from electronic cigarettes (ECIGs) is crucial for product regulation. Understanding nicotine delivery, and therefore efficacy and abuse potential, from ECIG products requires quantifying the total nicotine contained or emitted, as well as the partitioning between its free-base and protonated forms. To date, studies reporting nicotine content and emissions of ECIGs have not addressed whether the reported values correspond to the total nicotine or only one of its forms, making the reported results difficult to compare across studies, or to correlate against blood exposure measurements. In this study we investigate whether nicotine in ECIGs is indeed present in more than one form, whether measurements are affected by sampling media, and report a validated method for determining total, free-base (Nic) and protonated nicotine (NicH+) in ECIG liquids and aerosol emissions. Methods We developed an analytical method based on liquid-liquid extraction coupled with GC analysis to assess the respective amounts of Nic and NicH+. The method was first verified on pH-controlled solutions (5 < pH < 10) and then was applied to several ECIG liquids and aerosols generated using a smoking machine. Results The method showed high repeatability and efficiency, and the results were in agreement with theoretical predictions based on measured pH of the standard nicotine solutions. ECIG liquids and aerosols contained both Nic and NicH+, and their relative proportions varied widely. Free-base nicotine was found to account for 18-95% of the total nicotine depending on the product in question. Conclusions The wide variation in nicotine partitioning across products suggests that studies of nicotine delivery from ECIGs should account for this factor. A convenient method for analyzing nicotine fractions in electronic cigarettes has been demonstrated.

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

“…First, Stepanov and Fujioka, 19 Lisko et al, 20 and El-Hellani et al 8 all describe diluting an aliquot of e-liquid with water, measuring the pH, and then calculating α fb by eq 2. The result is that the values obtained suffer from both medium effects (water is different from an e-liquid) and dilution, though the pH values may, nevertheless, provide some useful relative indications of the overall acid/base balances in different e-liquids.…”

“…This problem is likely evidenced in the data of Lisko et al 20 (see Supporting Information). Second, El-Hellani et al 8 describe making 6 mL aqueous solutions of e-liquids, extracting with 6 mL toluene, and then determining nicotine in the toluene solvent extract as a measure of the nicotine percentage in the water. This approach suffers from the same dilution, medium, possible CO 2 incursion effects discussed above and introduces uncertainties regarding the extent to which the toluene extraction step affects the position of the NicH + ⇆ Nic + H + equilibrium in the aqueous dilution.…”

Online E-cigarette Marketing Claims: A Systematic Content and Legal Analysis

“…In the finalized deeming rule, the FDA stated that “labeling and advertising [for ENDS and other newly-deemed products] cannot be false or misleading, which will help reduce consumer confusion and misperception.” 17 As an example of a claim that may be “false or misleading,” some websites claim that the emissions from ENDS are “simply… water vapor” (Manufacturer: E Cigs Brand), even though numerous studies have shown that there are small amounts of concerning toxicants found in the emissions from ENDS. 32–36 Claims that lack scientific support or those that manipulate the science to overstate a product’s benefits may mislead consumers into purchasing and using ENDS products. 14 …”

Thermal Decomposition of Electronic Cigarette Liquid. Ir Study

“…The liquids for electronic cigarettes (ECIG) consist of nicotine (0-2% weight usually), propylene glycol, glycerol, distilled water and, optionally, flavors. In the aerosol composition produced by ECIG, the researcher found nicotine (both free base and protonated species) [16], tobacco-specific nitrosamines (in the case if they are in ECIG liquid initially) [17], diacetyl and acetyl propionyl (by the indirect method, presumably) [18], toluene, ethyl benzene, o-, m-, p-xylene [19], formaldehyde, acetaldehyde, acetone, propenal [20,21], glyoxal [22]. The data on vapors composition above ECIG liquids are not so large and detailed, and the call of F. Henkler and A. Luch «More extensive tests for e-cigarettes» outgoing from "Nature" pages [23] is fully justified.…”