An improved method was developed for the determination of the four major tobacco-specific nitrosamines(TSNAs) in mainstream cigarette smoke. The new method offers decreased sample preparation and analysis time as compared to traditional methods. This method uses isotope dilution liquid chromatography coupled with a tandem mass spectrometer with electrospray ionization and is significantly more sensitive than traditional methods. It also shows no evidence of artifactual formation of TSNAs.Sample concentrations were determined for four TSNAs in mainstream smoke using two isotopically labeled TSNAs analogues as internal standards. Mainstream smoke was collected on an industry standard 44-mm Cambridge filter pad, extracted with 0.1mol/L ammonium acetate, purified by solid-phase extraction, and analyzed without further sample cleanup. The analytical column is a 3.9mm×150mm Waters Symmertry Shield RP18 column and volume fraction of the mobile phase is 50% methanol, 50% water containing 0.1% acetic acid. The results show that the linear range is 0.5-100.0mg/L except for N-nitrosoanabasine (NAB) from 0.25 to 50.0mg/L. The limits of detection are 0.1mg/L for N-nitrosonornicotine (NNN), 0.08mg/L for 4-(methylnitrosamino)-1-(3-py-ridyl)-1-butanone (NNK), 0.05mg/L for N-nitrosoanatabine (NAT) and 0.06mg/L for NAB. The recoveries of the four TSNAs are from 90.2% to 105.7%.