Free-Base Nicotine Fraction αfb in Non-aqueous versus aqueous Solutions: Electronic Cigarette Fluids Without versus With Dilution with Water.

Introduction:
This text discusses the importance of understanding the acid-base chemistry in electronic cigarette (e-cigarette) fluids for designing and regulating e-cigarettes. The text develops a framework for predicting the fraction of nicotine in the free-base form (αfb) in e-liquids based on acid-nicotine ratios and overall acid-nicotine protonation constant values. It also highlights the limitations of measuring αfb values using methods that involve significant dilution with water.

Key Points:

* E-cigarettes' design and sensory properties are affected by nicotine's behavior in e-cigarette systems, which is influenced by acid-base characteristics of e-liquids.
* Two methods exist for probing acid-base chemistry in e-liquids and their aerosols: native solution methods (NSMs) and diluted solution methods (DSMs).
* NSMs provide a better understanding of the acid-base chemistry in unaltered e-liquids or aerosol liquids, while DSMs allow for the study of e-liquid composition when diluted with CO2-free water.
* Nicotine is a dibasic alkaloid that can exist in three forms: free-base (fb), monoprotonated (mp), and diprotonated (dp).
* The fraction of nicotine in the fb form (αfb) is affected by the level of protonating acid in the e-liquid, which impacts nicotine aerosol inhalation harshness and uptake kinetics.
* Common carboxylic acids used in e-liquids include benzoic acid and levulinic acid, while flavor chemicals like vanillin and ethyl vanillin are weak acids.
* The text combines acid-base chemical principles with recent data on nicotine protonation constants in PG/GL to develop a framework for predicting αfb values.

Main Message:
Understanding the acid-base chemistry in e-cigarette fluids is crucial for designing and regulating e-cigarettes. The text provides a framework for predicting αfb values based on acid-nicotine ratios and protonation constant values, highlighting the limitations of measuring αfb values using methods that involve significant dilution with water. Regulatory bodies should consider these factors when establishing guidelines for e-cigarette design and safety.

Pankow JF, Duell aK, Peyton Dh. Free-Base Nicotine Fraction αfb in Non-aqueous versus aqueous Solutions: Electronic Cigarette Fluids Without versus With Dilution with Water. Chemical research in toxicology. 2020;33(7):1729-1735. doi:10.1021/acs.chemrestox.0c00008