Minor Tobacco alkaloids as Biomarkers to Distinguish Combusted Tobacco Use From Electronic Nicotine Delivery Systems Use. Two New analytical Methods.

Introduction:
This article describes two new liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for quantifying minor tobacco alkaloids and a tobacco-specific nitrosamine metabolite in urine. These biomarkers can be used to distinguish between the use of combusted tobacco products and electronic nicotine delivery systems (ENDS). The study also discusses potential applications of these biomarkers in studies of ENDS use and dual use of ENDS and conventional tobacco products.

Key Points:

* The two new LC-MS/MS methods measure the minor tobacco alkaloids anabasine, anatabine, nicotelline, anatalline, and the tobacco-specific nitrosamine metabolite NNaL.
* The methods can be used to determine recent exposure to tobacco products and the extent of dual use of both products.
* The alkaloids are present in cigarette tobacco in concentrations ranging from about 1 to 1000 μg/g, while concentrations in most e-liquids used in ENDS are low due to purification processes.
* The first method is based on a published LC-MS/MS method for nicotelline and involves treating urine with titanium trichloride to convert N-oxides back to nicotelline.
* The second method utilizes a derivatization with hexanoic anhydride to enhance sensitivity and allows simultaneous determination of anabasine, anatabine, and NNaL.
* The two new methods can be useful in studies of dual use of ENDS and combusted cigarettes, as they can measure multiple biomarkers with a wide range of biological half-lives.
* The study also introduces the alkaloid anatalline as a new, highly selective biomarker for tobacco exposure.

Main Message:
The two new LC-MS/MS methods described in this article offer a viable approach to identifying and estimating the extent of tobacco product use in people using ENDS by using biomarkers specific to tobacco products. These methods can be useful in studies of dual use of ENDS and combusted cigarettes, as they can measure multiple biomarkers with a wide range of biological half-lives, and can also serve as a tool for regulatory agencies to monitor ENDS use and exposure to tobacco-derived harmful and potentially harmful constituents.

Jacob P, Chan L, Cheung P, et al. Minor Tobacco alkaloids as Biomarkers to Distinguish Combusted Tobacco Use From Electronic Nicotine Delivery Systems Use. Two New analytical Methods. Frontiers in chemistry. 2022;10:749089. doi:10.3389/fchem.2022.749089