Abstract
In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids.
Highlights
Nicotine is an alkaloid with a weakly basic nature
We present results using various analytical techniques that will facilitate the establishment of a standardized method by regulatory bodies for classifying e-liquids based on their free base nicotine yield
It can be argued that the purpose of the dilution approach is to provide a pH relevant scale for classifying e-liquids based on their free base nicotine yields
Summary
Nicotine is an alkaloid with a weakly basic nature. Based on the solvent nature, it can exist as protonated and free base nicotine. Tobacco companies have been using alkaline chemical substances such as ammonia or its related basic compounds in manufacturing of cigarettes [1, 2]. Based on the Pankow theory and studies by tobacco companies [3], free base nicotine is responsible for harshness or impact in smokers. Based on pH partition hypothesis of drug absorption [5], any drug penetrates biological membrane barrier in an unionized form. Erefore, free base nicotine is believed to cross the Journal of Analytical Methods in Chemistry biological membrane of the respiratory tract and lead to nicotine’s rapid absorption. Many authors, based on their in vitro and in vivo studies, have confirmed that rate of nicotine absorption is higher for basic than acidic nicotine solutions and aerosols [6,7,8,9,10]
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