Gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) with a triple quadrupole analyzer (QqQ) was applied for the first time to the determination of trace food-derived hazardous compounds in food samples. Thirteen heterocyclic amines were confirmed and quantified by the developed sensitive method. The method includes a solid-phase extraction procedure with a polystyrene copolymer cartridge (LiChrolut EN), followed by a derivatization reaction with N,N-dimethylformamide di-tert-butylacetal. Analyses were performed by gas chromatography with triple quadrupole mass spectrometry in the electron impact mode. The MS/MS fragmentation pathway of derived heterocyclic amines was studied and the differences of fragmentation characteristics were used successively to distinguish the isomers in absence of chemical standards. The excellent selectivity and sensitivity achieved in multiple reaction monitoring mode allowed us satisfactory quantitation and confirmation. The limits of quantitation of the method for these compounds ranged from 0.12 to 0.48ng/g of sample. The method developed was applied to the analysis of Chinese cooked foods, and the results demonstrated the potentiality of the GC-MS/MS method for the analysis of trace food-derived hazardous compounds in complex food matrices such as meat samples.