Under the Food, Drug, and Cosmetic Act (FD&C) all tobacco manufacturers and importers are required to report the levels of harmful and potentially harmful constituents (HPHCs) found in their tobacco products and tobacco smoke. Studies have reported the detection of up to 7000 different chemical components that can be inhaled through tobacco smoke such as nicotine, tar, nitrosamines, and polycyclic aromatic hydrocarbons. In 2012, the Food and Drug Administration (FDA) included in the Federal Register a list of 93 HPCHs suspected to be found in tobacco products and tobacco smoke. To support the Family Smoking Prevention and Tobacco Control Act, the National Institute of Standards and Technology has recently collaborated with the Center for Tobacco Products at the FDA to develop a new low nicotine tobacco filler Standard Reference Material (SRM 3222) to support the analysis of tobacco products. This new tobacco material has certified and reference mass fraction values for nicotine, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK), and moisture. In the current study, approximately 10 g of SRM 3222 was burned to produce tobacco smoke. Several different smoke collection apparatuses and organic solvents were evaluated to allow for the highest amount of tobacco smoke to be collected. After filtration, the homogenous solution was screened via gas chromatography/mass spectrometry for the identification of many HPHCs in the tobacco smoke.