Abstract: Tobacco-specific nitrosamines (TSNAs) are very important carcinogens in tobacco and cigarette smoke. In order to develop a robust analytical method to determine low levels of TSNAs in cigarette smoke, a dispersive solid phase extraction-UPLC-MS/MS method was used to simultaneously determine four TSNAs in mainstream cigarette smoke. Mainstream smoke was collected on a cambridge filter pad, further extracted with ammonium acetate aqueous solution, then cleaned up by primary secondary amine (PSA), and subsequently analyzed with UPLC-MS/MS. The proposed method displayed limit of detections between 0.008 and 0.016 ng/mL and good linearity over the range from 1 to 110 ng/mL, with a R²>0.99. Recovery varied from 82.5% to 94.8% for Chinese Virginia cigarettes. Mean precisions ranged from 4.9%-9.8%. The proposed method, which provides higher sensitivity and specificity, is suitable for quantitatively analyzing TSNAs yield in Chinese Virginia cigarettes.