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      Isotope-Dilution Gas Chromatography-Mass Spectrometry Method for the Selective Detection of Nicotine and Menthol in E-Cigarette, or Vaping, Product Liquids and Aerosols

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          Abstract

          We developed a quantitative method for analyzing nicotine and menthol in e-cigarette, or vaping, products (EVPs). These products may adversely impact health through inhalational exposure to addictive and harmful chemicals. The presence of unknown substances in do-it-yourself e-liquids, counterfeits, or unregulated products may increase exposure to harmful chemicals, as underscored by the 2019 EVP use-associated lung injury (EVALI) outbreak. To minimize these risks, it is important to accurately quantify nicotine and menthol in e-liquids and aerosol emissions to evaluate EVP authenticity, verify product label accuracy, and identify potentially hazardous products. We developed a simple, versatile, high-throughput method using isotope-dilution gas chromatography-mass spectrometry for quantifying nicotine and menthol concentrations in both e-liquid contents and machine-generated aerosol emissions of EVPs. Rigorous validation has demonstrated that the method is specific, precise (CV<2.71%), accurate (percent error ≤7.0%), and robust. Linear calibration ranges from 0.01 to 1.00 mg/ml for both analytes was achieved, corresponding to expected analyte levels in e-liquids and machine-generated EVP aerosols. Limits of detection (LODs) in the final 10-ml sample extract were 0.4 μg/ml for nicotine and 0.2 μg/ml for menthol. The method was used to analyze aerosol emissions of 141 EVPs associated with the 2019 EVALI outbreak; detectable levels of nicotine (2.19–59.5 mg/g of aerosol) and menthol (1.09–10.69 mg/g of aerosol) were observed in 28 and 11%, respectively, of the samples analyzed. Nicotine was not detected in any of the tetrahydrocannabinol (THC), cannabidiol (CBD), or oil-based products, while menthol (2.95 mg/g of aerosol) was only detected in one of these products (THC-labeled). The analytical method can be used to quantify nicotine and menthol concentrations in the e-liquids and aerosols from a range of EVPs, and these findings highlight a difference between e-cigarette and other vaping products.

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          Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI

          The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.
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            E-cigarette Use Among Middle and High School Students — United States, 2020

            The use of any tobacco product by youths is unsafe, including electronic cigarettes (e-cigarettes) (1). Most e-cigarettes contain nicotine, which is highly addictive, can harm the developing adolescent brain, and can increase risk for future addiction to other drugs (1). E-cigarette use has increased considerably among U.S. youths since 2011 ( 1 , 2 ). Multiple factors have contributed to this increase, including youth-appealing flavors and product innovations ( 1 – 3 ). Amid the widespread use of e-cigarettes and popularity of certain products among youths, on February 6, 2020, the Food and Drug Administration (FDA) implemented a policy prioritizing enforcement against the manufacture, distribution, and sale of certain unauthorized flavored prefilled pod or cartridge-based e-cigarettes (excluding tobacco or menthol).* CDC and FDA analyzed nationally representative data from the 2020 National Youth Tobacco Survey (NYTS),† a cross-sectional, school-based, self-administered survey of U.S. middle school (grades 6–8) and high school (grades 9–12) students conducted during January 16–March 16, 2020. § The NYTS study protocol was approved by the CDC institutional review board. Current (past 30-day) e-cigarette use was assessed, overall and by device ¶ and flavor** type. Weighted prevalence estimates and population totals †† were calculated. Analyses were conducted using SAS-callable SUDAAN (version 11.0.3; RTI International). In 2020, 19.6% of high school students (3.02 million) and 4.7% of middle school students (550,000) reported current e-cigarette use. Among current e-cigarette users, 38.9% of high school students and 20.0% of middle school students reported using e-cigarettes on 20 or more of the past 30 days; 22.5% of high school users and 9.4% of middle school users reported daily use. Among all current e-cigarette users, 82.9% used flavored e-cigarettes, including 84.7% of high school users (2.53 million) and 73.9% of middle school users (400,000). Among high school current e-cigarette users, the most commonly used device type was prefilled pods or cartridges (48.5%; 1.45 million), followed by disposables (26.5%; 790,000), and tanks (14.8%; 440,000). Among middle school current e-cigarette users, the most commonly used device type was prefilled pods or cartridges (41.3%; 220,000), followed by tanks (21.5%; 110,000), and disposables (15.2%; 80,000). Among high school students who currently used any type of flavored e-cigarettes, the most commonly used flavor types were fruit (73.1%; 1.83 million); mint (55.8%; 1.39 million); menthol (37.0%; 920,000); and candy, desserts, or other sweets (36.4%; 910,000). Among middle school students who currently used any type of flavored e-cigarettes, the most commonly used flavor types were fruit (75.6%; 290,000); candy, desserts, or other sweets (47.2%; 180,000); mint (46.5%; 180,000); and menthol (23.5%; 90,000). Among current users of flavored prefilled pods or cartridges, the most commonly used flavor types were fruit (66.0%; 920,000); mint (57.5%; 800,000); menthol (44.5%; 620,000); and candy, desserts, or other sweets (35.6%; 490,000) (Figure). Among current users of flavored disposable e-cigarettes, the most commonly used flavor types were fruit (82.7%; 650,000), mint (51.9%; 410,000); candy, desserts, or other sweets (41.7%; 330,000); and menthol (23.3%; 180,000). FIGURE Percentage of flavor types used by current (past 30-day) flavored e-cigarette users among U.S. middle and high school students,* by device type†, § — National Youth Tobacco Survey, United States, 2020 * Flavor type use among current (past 30-day) users of flavored e-cigarettes was determined by answers to the question “What flavors were the e-cigarettes that you have used in the past 30 days? (Select one or more).” Response options were “menthol,” “mint,” “clove or spice,” “fruit,” “chocolate,” “alcoholic drinks (such as wine, cognac, margarita, or other cocktails),” “candy, desserts, or other sweets,” and “some other flavor not listed here” (write-in responses were not assessed). Data for “clove or spice” are not shown because of statistically unreliable estimates due to unweighted denominator 30% across all device types. † Device type use among current e-cigarette users was determined by answers to the question “Which of the following best describes the type of e-cigarette you have used in the past 30 days? If you have used more than one type, please think about the one you use most often.” Response options were “a disposable e-cigarette,” “an e-cigarette that uses pre-filled pods or cartridges (e.g., JUUL),” “an e-cigarette with a tank that you refill with liquids,” “a mod system (an e-cigarette that can be customized by the user with their own combination of batteries or other parts),” and “I don’t know the type.” § The following data were statistically unreliable and not shown due to unweighted denominator 30%: use of chocolate flavor types among current flavored e-cigarette users of disposable e-cigarettes, mod systems, or those who reported “I don’t know the type” for device type; alcoholic drink flavor types among current flavored e-cigarette users of mod systems or those who reported “I don’t know the type” for device type; and “some other flavor” among current flavored e-cigarette users who reported “I don’t know the type” for device type. The figure is a bar chart showing the percentage of flavor types used by current (past 30-day) flavored e-cigarette users among U.S. middle and high school students, by device type in the United States during 2020 according to the National Youth Tobacco Survey. In 2020, approximately one in five high school students and one in 20 middle school students currently used e-cigarettes. By comparison, in 2019, 27.5% of high school students (4.11 million) and 10.5% of middle school students (1.24 million) reported current e-cigarette use ( 2 ). Although these data reflect a decline in current e-cigarette use since 2019, 3.6 million U.S. youths still currently used e-cigarettes in 2020, and among current users, more than eight in 10 reported using flavored e-cigarettes. Consistent with 2019, prefilled pods or cartridges were the most commonly used device type in 2020; however, during 2019–2020, disposable e-cigarette use increased approximately 1,000% (from 2.4% to 26.5%) among high school current e-cigarette users and approximately 400% (from 3.0% to 15.2%) among middle school current e-cigarette users. Although use of fruit flavored e-cigarettes was common among users in 2020, findings also suggest prominent menthol e-cigarette use, including among nearly one half of flavored prefilled pod or cartridge users and one quarter of flavored disposable product users. Comprehensive implementation of evidence-based strategies at the national, state, and local levels, in coordination with FDA regulation, can prevent and reduce youth tobacco product use ( 1 , 4 , 5 ). Strategies to address factors driving youth e-cigarette use are particularly critical. In addition to FDA’s enforcement policy that prohibits the sale of prefilled pod or cartridge-based e-cigarettes in any flavor other than tobacco or menthol, several states and communities have restricted all flavored e-cigarette sales, including menthol. §§
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              A multi-rule Shewhart chart for quality control in clinical chemistry.

                Author and article information

                Contributors
                Journal
                Front Chem
                Front Chem
                Front. Chem.
                Frontiers in Chemistry
                Frontiers Media S.A.
                2296-2646
                27 September 2021
                2021
                : 9
                : 754096
                Affiliations
                Tobacco Products Laboratory, Tobacco and Volatiles Branch, Division of Laboratory Sciences, National Center for Environmental Health, U.S. Centers for Disease Control and Prevention, Atlanta, GA, United States
                Author notes

                Edited by: Marta Concheiro-Guisan, John Jay College of Criminal Justice, United States

                Reviewed by: Yi He, John Jay College of Criminal Justice, United States

                Chengbin Zheng, Sichuan University, China

                *Correspondence: José J. Pérez, JPerez1@ 123456cdc.gov

                This article was submitted to Analytical Chemistry, a section of the journal Frontiers in Chemistry

                Article
                754096
                10.3389/fchem.2021.754096
                8503638
                f4851c30-f06e-4c1a-ac15-81d75f373fba
                Copyright © 2021 Pérez, Watson, Blount and Valentín-Blasini.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 05 August 2021
                : 14 September 2021
                Categories
                Chemistry
                Original Research

                e-cigarettes,vapes,nicotine,menthol,gas chromatography-mass spectrometry

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