{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:35:42Z","timestamp":1758404142308,"version":"3.41.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>E-cigarette, or vaping, product (EVP) use has increased dramatically in the United States over the last 4\u00a0years, particularly in youth and young adults. Little information is available on the chemical contents of these products. Typically, EVPs contain an active ingredient such as nicotine, CBD, or THC dissolved in a suitable solvent that facilitates aerosol generation. One EVP solvent, vitamin E acetate (VEA), has been measured in EVP liquids associated with lung injury. However, no validated analytical methods for measuring VEA in the aerosol from these devices was previously available. Therefore, we developed a high throughput isotope dilution LC-MS\/MS method to simultaneously measure VEA and three other related tocopherols in aerosolized EVP samples. The assay was precise, with VEA repeatability ranging from 4.0 to 8.3% and intermediate precision ranging from 2.5 to 6.7%. Similar precision was obtained for the three other tocopherols measured. The LODs for the four analytes ranged from 8.85 \u00d7 10<jats:sup>\u22126<\/jats:sup> to 2.28 \u00d7 10<jats:sup>\u22125<\/jats:sup>\u00a0\u03bcg analyte per mL of aerosol puff volume, and calibration curves were linear (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> &amp;gt; 0.99). This method was used to analyze aerosol emissions of 147 EVPs associated with EVALI case patients. We detected VEA in 46% of the case-associated EVPs with a range of 1.87 \u00d7 10<jats:sup>\u22124<\/jats:sup>\u201374.1\u00a0\u00b5g per mL of aerosol puff volume and mean of 25.1\u00a0\u00b5g per mL of aerosol puff volume. Macro-levels of VEA (&amp;gt;0.1% w\/w total aerosol particulate matter) were not detected in nicotine or cannabidiol (CBD) products; conversely 71% of the EVALI associated tetrahydrocannabinol (THC) products contained macro-levels of VEA. Trace levels of other tocopherol isoforms were detected at lower rates and concentrations (\u03b1-tocopherol: 41% detected, mean 0.095\u00a0\u00b5g analyte per mL of aerosol puff volume; \u03b3-tocopherol: 5% detected, mean 0.0193\u00a0\u00b5g analyte per mL of aerosol puff volume; \u03b4-tocopherol: not detected). Our results indicate that VEA can be efficiently transferred to aerosol by EVALI-associated EVPs vaped using a standardized protocol.<\/jats:p>","DOI":"10.3389\/fchem.2021.730954","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T07:09:15Z","timestamp":1628147355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Development, Validation, and Application of a Novel Method for the Analysis of Vitamin E Acetate and Other Tocopherols in Aerosol Emissions of E-Cigarettes, or Vaping Products Associated With Lung Injury"],"prefix":"10.3389","volume":"9","author":[{"given":"Andrew","family":"Puetz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Morel Espinosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin C.","family":"Blount","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liza","family":"Valent\u00edn-Blasini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.1468-2494.2009.00514.x","article-title":"Determination of Tocopheryl Acetate and Ascorbyl Tetraisopalmitate in Cosmetic Formulations by HPLC","volume":"31","author":"Almeida","year":"2009","journal-title":"HPLC"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1056\/nejmc2000231","article-title":"An Animal Model of Inhaled Vitamin E Acetate and EVALI-like Lung Injury","volume":"382","author":"Bhat","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e012742","DOI":"10.1161\/jaha.119.012742","article-title":"Is There A Role for Electronic Cigarettes in Tobacco Cessation?","volume":"8","author":"Bhatnagar","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.15585\/mmwr.mm6845e2","article-title":"Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E-Cigarette, or Vaping, Product Use-Associated Lung Injury - 10 States, August-October 2019","volume":"68","author":"Blount","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1056\/nejmoa1916433","article-title":"Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI","volume":"382","author":"Blount","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1007\/s12161-012-9452-0","article-title":"A Fast HPLC Method for Determination of Vitamin E Acetate in Dietary Supplements Using Monolithic Column","volume":"6","author":"Brabcov\u00e1","year":"2013","journal-title":"Food Anal. Methods"},{"key":"B7","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.aca.2007.01.049","article-title":"Determination of Tocopherols and Tocotrienols in Cereals by Pressurized Liquid Extraction-Liquid Chromatography-Mass Spectrometry","volume":"587","author":"Bustamante-Rangel","year":"2007","journal-title":"Analytica Chim. Acta"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1056\/nejmc1913069","article-title":"Pathology of Vaping-Associated Lung Injury","volume":"381","author":"Butt","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1016\/j.bbamem.2012.05.024","article-title":"Role of Lipid Ordered\/disordered Phase Coexistence in Pulmonary Surfactant Function","volume":"1818","author":"Casals","year":"2012","journal-title":"Biochim. Biophys. Acta (Bba) - Biomembranes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1002\/sim.3222","article-title":"Multi-rule Quality Control for the Age-Related Eye Disease Study","volume":"27","author":"Caudill","year":"2008","journal-title":"Statist. Med."},{"key":"B11","unstructured":"Electronic Cigarettes (E-cigarettes)"},{"key":"B12","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/B978-0-12-378612-8.00431-5","article-title":"Nutriential Hazards: Micronutrients: Vitamins and Minerals","volume-title":"Encyclopedia of Food Safety","author":"Cilla","year":"2014"},{"year":"","key":"B13","article-title":"Routine analytical machine for e-cigarette aerosol generation and collection-definition and standard conditions"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4517","DOI":"10.3390\/molecules24244517","article-title":"Simultaneous LC\/MS Analysis of Carotenoids and Fat-Soluble Vitamins in Costa Rican Avocados (Persea Americana Mill.)","volume":"24","author":"Cort\u00e9s-Herrera","year":"2019","journal-title":"Molecules"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.15585\/mmwr.mm6845a2","article-title":"Tobacco Product Use and Cessation Indicators Among Adults - United States, 2018","volume":"68","author":"Creamer","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1021\/jf053102n","article-title":"Quantification of Tocopherols and Tocotrienols in Portuguese Olive Oils Using HPLC with Three Different Detection Systems","volume":"54","author":"Cunha","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"B17","unstructured":"Journey of a Tainted Cartridge; From China's Labs to Your Lungs\n          \n            DownsD.\n            DavidH.\n            BarcottBruce."},{"key":"B18","unstructured":"Vape Pen Lung Injury: Here's what You Need to Know\n            DownsD."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/toxics8010008","article-title":"Analysis of Cannabinoid-Containing Fluids in Illicit Vaping Cartridges Recovered from Pulmonary Injury Patients: Identification of Vitamin E Acetate as a Major Diluent","volume":"8","author":"Duffy","year":"2020","journal-title":"Toxics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1097\/mcp.0000000000000348","article-title":"Electronic Cigarettes as Smoking Cessation Tool","author":"Ghosh","year":"2017"},{"key":"B21","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/nejmoa1808779","article-title":"A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy","volume":"380","author":"Hajek","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B22","unstructured":"New York State Department of Health announces update on investigation into vaping-associated pulmonary illnesses: department warns against use of black-market vaping products: lab test results show high levels of vitamin E acetate, now focus of investigation\n            HealthN. Y. S. D. O.\n          2019"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/j.chest.2020.03.085","article-title":"Vaping-Related Acute Parenchymal Lung Injury","volume":"158","author":"Jonas","year":"2020","journal-title":"Chest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1016\/j.bbamem.2012.06.016","article-title":"Modulated Phases of Phospholipid Bilayers Induced by Tocopherols","volume":"1818","author":"Kamal","year":"2012","journal-title":"Biochim. Biophys. Acta (Bba) - Biomembranes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.chroma.2007.04.058","article-title":"Comparison of Reversed-phase Liquid Chromatography-Mass Spectrometry with Electrospray and Atmospheric Pressure Chemical Ionization for Analysis of Dietary Tocopherols","volume":"1157","author":"Lanina","year":"2007","journal-title":"J. Chromatogr. A"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.15585\/mmwr.mm6849e1","article-title":"Update: Demographic, Product, and Substance-Use Characteristics of Hospitalized Patients in a Nationwide Outbreak of E-Cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, December 2019","volume":"68","author":"Lozier","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B27","unstructured":"Food and Drug Administration"},{"key":"B28","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1165\/rcmb.2020-0209oc","article-title":"Dose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate","volume":"63","author":"Matsumoto","year":"2020","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B29","unstructured":"CBS News, These states now have legal weed, and which states could follow suit in 2020\n          \n            McnamaraA.\n          2020"},{"key":"B30","doi-asserted-by":"publisher","first-page":"985","DOI":"10.15585\/mmwr.mm6843e1","article-title":"Update: Characteristics of Patients in a National Outbreak of E-Cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019","volume":"68","author":"Moritz","year":"2019","journal-title":"MMWR Morb Mortal Wkly Rep."},{"key":"B31","first-page":"353","article-title":"Analysis of Vitamin E in Commercial Cosmetic Preparations by HPLC","volume":"61","author":"Nada","year":"2010","journal-title":"J. Cosmet. Sci."},{"key":"B32","unstructured":"State Medical Marijuana Laws"},{"key":"B33","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.cotox.2019.05.001","article-title":"Impact of Electronic Cigarette Aerosols on Pregnancy and Early Development","volume":"14","author":"Orzabal","year":"2019","journal-title":"Curr. Opin. Toxicol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev-clinpsy-032816-045128","article-title":"Medical Marijuana and Marijuana Legalization","volume":"13","author":"Pacula","year":"2017","journal-title":"Annu. Rev. Clin. Psychol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s12161-018-1331-x","article-title":"A Fast and Simple Method for Determination of Vitamin E in Infant Formula by Dispersive Liquid-Liquid Microextraction Combined with HPLC-UV","volume":"12","author":"Sadrykia","year":"2019","journal-title":"Food Anal. Methods"},{"key":"B36","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/chromsci\/bmr032","article-title":"Determination of Vitamin E Isomers of Grape Seeds by High-Performance Liquid Chromatography-UV Detection","volume":"50","author":"Seker","year":"2012","journal-title":"J. Chromatogr. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"390","DOI":"10.7326\/m16-1107","article-title":"Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users","volume":"166","author":"Shahab","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3420","DOI":"10.1111\/ajt.15690","article-title":"Update: Interim Guidance for Health Care Providers Evaluating and Caring for Patients with Suspected E\u2010cigarette, or Vaping, Product Use Associated Lung Injury - United States, October 2019","volume":"19","author":"Siegel","year":"2019","journal-title":"Am. J. Transpl."},{"volume-title":"Quality Assurance of Chemical Measurements","year":"1987","author":"Taylor","key":"B39"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.15585\/mmwr.mm6937e1","article-title":"E-cigarette Use Among Middle and High School Students - United States, 2020","volume":"69","author":"Wang","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"6349","DOI":"10.1073\/pnas.1920925117","article-title":"Potential for Release of Pulmonary Toxic Ketene from Vaping Pyrolysis of Vitamin E Acetate","volume":"117","author":"Wu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B42","unstructured":"Contaminant Analysis of Illicit vs Regulated Market Extracts\n            Zachary EisenbergD. M.\n            LamVu.\n            ChengCathy.\n            RichardJosh.\n            BurackBenjamin.\n          2019"},{"key":"B43","doi-asserted-by":"publisher","first-page":"iii3","DOI":"10.1136\/tobaccocontrol-2014-051670","article-title":"Four Hundred and Sixty Brands of E-Cigarettes and Counting: Implications for Product Regulation","volume":"23","author":"Zhu","year":"2014","journal-title":"Tob. Control."}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2021.730954\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T07:09:49Z","timestamp":1628147389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2021.730954\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,5]]},"references-count":43,"alternative-id":["10.3389\/fchem.2021.730954"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2021.730954","relation":{},"ISSN":["2296-2646"],"issn-type":[{"type":"electronic","value":"2296-2646"}],"subject":[],"published":{"date-parts":[[2021,8,5]]},"article-number":"730954"}}