The US FDA Center for Tobacco Products is currently collecting data on mainstream cigarette smoke constituents, but it is not clear how this will impact future product testing requirements. To allow for maximum flexibility in our laboratory we have tried to develop analytical methods to analyze a wide range of compounds using only a few instrument types. The US FDA Tobacco Products Scientific Advisory Committee (TPSAC) proposed HPHC list includes at least 93 compounds in mainstream smoke; over 50% can be analyzed by gas chromatography combined with mass spectrometry (GC-MS). In our laboratory we use GC-MS to measure volatile, semi-volatile and polycyclic compounds. We will present separate methods for the application of a tandem GC-MS/MS system for the analysis of nitrosamines, N-nitrosodiethanolamine (NDELA), aromatic amines, and large polycyclic aromatic hydrocarbons including dibenzopyrenes in mainstream smoke. These methods have several advantages including simple sample cleanup and/or greatly reduced limits of detection. All compounds were separated on an Agilent 7890 GC system using an HP-5MS column followed by detection on an Agilent 7000 QQQ tandem mass spectrometer. For the determination of nitrosamines, the mass spectrometer was operated in positive chemical ionization mode using ammonia as the reagent gas. NDELA, 1-Aminonaphthalene, 2-Aminonaphthalene, 4-Aminobiphenyl, o-Anisidine, o-Toluidine, and 2,6-Dimethylaniline were derivatized prior to analysis. Detection for all compounds was performed using multiple reaction monitoring (MRM). All compounds gave levels of detection of less than 1 ng/mL. Method validation information will be presented for all compounds including calibration range, method reproducibility, and other analytical details.