Abstract: For fast and accurately determining the tobacco-specific nitrosamines (TSNAs) in mainstream cigarette smoke,the test for improving the determining conditions of liquid chromatography-tandem mass spectrometry was conducted.The results showed that:1) 10 mmol/L of ammonium acetate solution could replace 100 mmol/L of ammonium acetate solution as an extractant;2) the sample extraction could be directly analyzed by LC-MS/MS after it was filtered by 0.45 μm membrane; 3) more accurate quantitative results were obtainable by simultaneously using NNN-d₄,NNK-d₄,NAT-d₄,and NAB-d₄ as internal standards;4) the recoveries of the TSNAs ranged from 91% to 100.6% with the RSDs of 0.76% to 5.42% and the limits of detection of 0.06 to 0.14 ng/mL.The method can be used to determine the contents of TSNAs in mainstream smoke of Virginia or blended type cigarettes.