An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids

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. T...

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Main Authors: Vinit V. Gholap, Rodrigo S. Heyder, Leon Kosmider, Matthew S. Halquist
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Analytical Methods in Chemistry
Online Access:http://dx.doi.org/10.1155/2020/6178570
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author Vinit V. Gholap
Rodrigo S. Heyder
Leon Kosmider
Matthew S. Halquist
author_facet Vinit V. Gholap
Rodrigo S. Heyder
Leon Kosmider
Matthew S. Halquist
author_sort Vinit V. Gholap
collection DOAJ
description 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.
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spelling doaj-art-293f56124b4844c7bb27fe0c8450f81c2025-02-03T06:43:26ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732020-01-01202010.1155/2020/61785706178570An Analytical Perspective on Determination of Free Base Nicotine in E-LiquidsVinit V. Gholap0Rodrigo S. Heyder1Leon Kosmider2Matthew S. Halquist3Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond 23298, VA, USADepartment of Pharmaceutics, Pharmaceutical Engineering, School of Pharmacy, Virginia Commonwealth University, Richmond 23298, VA, USADepartment of General and Inorganic Chemistry, Medical University of Silesia, Katowice FOPS in Sosnowiec, Jagiellonska 4, 41-200 Sosnowiec, PolandDepartment of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond 23298, VA, USAIn 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.http://dx.doi.org/10.1155/2020/6178570
spellingShingle Vinit V. Gholap
Rodrigo S. Heyder
Leon Kosmider
Matthew S. Halquist
An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
Journal of Analytical Methods in Chemistry
title An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
title_full An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
title_fullStr An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
title_full_unstemmed An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
title_short An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids
title_sort analytical perspective on determination of free base nicotine in e liquids
url http://dx.doi.org/10.1155/2020/6178570
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