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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2020-01-01
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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 |
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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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