ABSTRACT – LABORATORY CORE The YCSTP’s goal is to reduce tobacco use and addiction. By understanding better how tobacco product constituents such as coolants, flavorants, sweeteners, nicotine source (natural vs. synthetic) and nicotine enantiomer (S- vs. R-) ratio influence appeal, we aim to inform the FDA about the risk of nicotine addiction and harm. Optimal interpretation of the study outcomes requires that key chemical components are accurately quantified in tobacco products and in biological samples from the study participants. The main objective of the Laboratory Core is to provide accurate, reproducible, and timely characterization and quantification of such components in support of the projects and pilots of the Center, as well as to create custom e-liquids when necessary. The core will attain its objective by pursuing five specific aims. (1) To identify and accurately quantify chemicals in tobacco products and in vapors produced from them, such as nicotine (including R- and S- enantiomers), synthetic coolants and menthol, flavorants, sweeteners, and other compounds of interest. (2) To generate objective and quantitative estimates of exposure to, and harm from, tobacco products by measuring the following biomarkers in biological samples: nicotine, cotinine, 3-hydroxy cotinine, total nicotine equivalents, nicotelline, menthol glucuronide, and NNAL (4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol). (3) To maintain a database of tobacco product constituents, such as flavorants, coolants, and sweeteners. (4) To create custom e-liquids for ongoing studies when commercial products are not available due to market changes. (5) To maintain a repository of biological samples obtained from the study participants. The core will also be able to set up other assays, as mandated by the evolving needs of the center. Over the past 9 years, this core has significantly advanced knowledge about tobacco product constituents, including novel ones, and particularly how these constituents contribute to addiction and harm. The core will be successful because: (a) many of the chemical assays necessary for aims 1 and 2 are validated and ready for immediate use, (b) the core has an extensive track record of detecting novel tobacco product constituents of concern, (c) the core has the necessary expertise, facilities and equipment to set up new assays in a timely fashion, (d) the database (aim 3) and biorepository (aim 5) are already in place and can readily be expanded to accommodate the data and samples obtained from the new projects, and (e) the core has experience in creating custom e-liquids (aim 4). By providing these services reliably to the YCSTP, the Laboratory Core will contribute critically toward the success of YCSTP’s TCORS 3.0 projects, which will ultimately aid in informing the FDA on the risk of nicotine addiction in new products and constituents.