Abstract: In order to investigate the puff-by-puff release characteristics of gas phase of mainstream cigarette smoke(MSS),an atmospheric pressure chemical ionization tandem mass spectrometry(APCI-MS/MS) method was developed for on-line analysis of seven organic compounds,including acrylonitrile,acrolein, crotonaldehyde,benzene,toluene,pyridine and styrene,in gas phase of MSS.A smoking machine was modified to couple with an APCI-MS ion source,after passing through a Cambridge filter,the gas phase of MSS was directly introduced into the APCI-MS ion source for analysis.The results showed that:The calibration curves of the organic compounds exhibited good linear relations(R²>0.99) with the limits of detection from 0.016 to 2.05 ng/mL and the relative standard deviations(RSDs) from 2.63% to 8.89%.The single puff and total yields of the said organic compounds differed tremendously,and did the puff-by-puff release characteristics of the organic compounds.This method is simple,fast,sensitive,repeatable and suitable for the investigation of puff-by-puff release characteristics of MSS.