{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:50:25Z","timestamp":1782258625369,"version":"3.54.5"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"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>Nicotine is a chiral alkaloid; nitrogen-containing organic compound that occurs naturally. (S)-nicotine is extracted from Tobacco plants and used as the key addictive ingredient in many smoking products. Synthetic nicotine has gained the interest of many smoking product manufacturers over the last few decades due to the ease and low cost of manufacturing. Another claimed advantage of synthetic nicotine is the absence of genotoxic impurities that form during the extraction process of nicotine. These impurities are other plant alkaloids, phenolic compounds, and heavy metals. Additionally, the U. S. FDA has implemented new regulations on the quality control of synthetic nicotine. However, only a very few research articles have been published on assessing the complete impurity profile of synthetic nicotine. Therefore, the need to know the composition difference between tobacco-extracted nicotine vs. synthetic nicotine is highly necessary. In this research study, the impurity profile of thirteen different lots of synthetic nicotine was compared with fourteen lots of nicotine extracted from plants using in-house analytical methods. First, the samples were tested for other alkaloids and phenols by reversed-phase High-Performance Liquid Chromatography (HPLC). Second, the chiral purity was analyzed by normal phase HPLC. Third, lead and arsenic content were tested by atomic absorption and fluorescence spectrometry. Fourth, nicotine-specific nitrosamines were tested by LC-MS. The reversed phase HPLC data suggested similar quantities of total impurities in both synthetic and tobacco-extracted nicotine (0.1%). However, synthetic nicotine lacks some impurities such as cotinine, nornicotine, and nicotine-N-oxide. Additionally, the synthetic nicotine lots used in this study have high enantiomeric purity similar to the tobacco-extracted nicotine.<\/jats:p>","DOI":"10.3389\/fchem.2024.1483868","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T13:56:49Z","timestamp":1728914209000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparison of genotoxic impurities in extracted nicotine vs. synthetic nicotine"],"prefix":"10.3389","volume":"12","author":[{"given":"Ayesha","family":"Nisathar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3390\/separations8060077","article-title":"Determination of nicotine-related impurities in nicotine pouches and tobacco-containing products by liquid chromatography\u2013tandem mass spectrometry","volume":"8","author":"Avagyan","year":"2021","journal-title":"Separations"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0267049","DOI":"10.1371\/journal.pone.0267049","article-title":"Analysis and differentiation of tobaccoderived and synthetic nicotine products: addressing an urgent regulatory issue","volume":"17","author":"Cheetham","year":"2022","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1021\/acs.chemrestox.8b00097","article-title":"Free-base nicotine determination in electronic cigarette liquids by 1H NMR spectroscopy","volume":"31","author":"Duell","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1021\/acs.chemrestox.5b00107","article-title":"Free-base and protonated nicotine in electronic cigarette liquids and aerosols","volume":"28","author":"El-Hellani","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/6178570","article-title":"An analytical perspective on determination of free base nicotine in E-liquids","volume":"2020","author":"Gholap","year":"2020","journal-title":"J. Anal. Methods Chem."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-540-69248-5","volume-title":"Handbook of experimental pharmacology, Nicotine psychopharmacology","author":"Henningfield","year":"2009"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e113","DOI":"10.1136\/tobaccocontrol-2021-056626","article-title":"Synthetic nicotine has arrived","volume":"32","author":"Jordt","year":"2023","journal-title":"Tob. Control. NLM (Medline)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.fct.2018.05.008","article-title":"Tobacco-specific nitrosamines: a literature review","volume":"118","author":"Konstantinou","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/tc-2023-057928","article-title":"Synthetic nicotine descriptors: awareness and impact on perceptions of e-cigarettes among US youth","author":"Kowitt","year":"2023","journal-title":"Tob. Control"},{"key":"B10","unstructured":"Method for Synthesizing (S)-Nicotine. European Patent: EP 4119671A1\n            LinW.\n          2023"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1093\/ntr\/ntu279","article-title":"Chemical composition and evaluation of nicotine, tobacco alkaloids, PH, and selected flavors in E-cigarette cartridges and refill solutions","volume":"17","author":"Lisko","year":"2015","journal-title":"Nicotine Tob. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.17957\/IJAB\/15.1026","article-title":"Influence of nicotine released in soils to the growth of subsequent maize crop, soil bacteria and fungi","author":"Lisuma","year":"2019","journal-title":"Int. J. Agric. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"102222","DOI":"10.1016\/j.pmedr.2023.102222","article-title":"Synthetic nicotine E-liquids sold in US online vape shops","volume":"1","author":"Ma","year":"2023","journal-title":"Prev. Med. Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1021\/tx020050c","article-title":"Fraction of free-base nicotine in fresh smoke particulate matter from the eclipse \u201ccigarette\u201d by 1H NMR spectroscopy","volume":"16","author":"Pankow","year":"2003","journal-title":"Chem. Res. Toxicol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1093\/jat\/bku013","article-title":"Toxic metal concentrations in mainstream smoke from cigarettes available in the USA","volume":"38","author":"Pappas","year":"2014","journal-title":"J. Anal. Toxicol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/bf02247412","article-title":"The role of nicotine in tobacco use","volume":"108","author":"Robinson","year":"1992","journal-title":"Psychopharmacology (Berl)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1021\/es049038s","article-title":"Source and health implications of high toxic metal concentrations in illicit tobacco products","volume":"39","author":"Stephens","year":"2005","journal-title":"Environ. Sci. Technol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"613","DOI":"10.3390\/ijerph8020613","article-title":"Hazardous compounds in tobacco smoke","volume":"8","author":"Talhout","year":"2011","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"16263","DOI":"10.1038\/s41598-020-73385-6","article-title":"Effect of free-base and protonated nicotine on nicotine yield from electronic cigarettes with varying power and liquid vehicle","volume":"10","author":"Talih","year":"2020","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s13105-016-0465-9","article-title":"Tobacco nitrosamines as culprits in disease: mechanisms reviewed","volume":"72","author":"Yalcin","year":"2016","journal-title":"J. Physiology Biochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"8087","DOI":"10.1021\/acs.est.8b01533","article-title":"Cigarette smoking: an assessment of tobacco\u2019s global environmental footprint across its entire supply chain","volume":"52","author":"Zafeiridou","year":"2018","journal-title":"Environ. Sci. Technol."}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1483868\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T13:56:54Z","timestamp":1728914214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1483868\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":21,"alternative-id":["10.3389\/fchem.2024.1483868"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2024.1483868","relation":{},"ISSN":["2296-2646"],"issn-type":[{"value":"2296-2646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"article-number":"1483868"}}