A simple and specific method able to identify and quantify traces of 14 sulfonamide antibacterials (SAs) in milk and eggs is presented. This method uses a single solid-phase extraction (SPE) cartridge for simultaneous extraction and purification of SAs in the above matrices. Milk and egg samples are passed through a Carbograph 4 sorption cartridge. After analyte desorption, an aliquot of the final extract is injected into a liquid chromatography-mass spectrometry (LC-MS) instrument equipped with an electrospray ion source (ESI) and a single quadrupole. MS data acquisition is performed in the positive-ion mode and by a time-scheduled multiple-ion selected ion monitoring program. Compared to two published methods, the present protocol extracted larger amounts of SAs from both milk and egg and decreased the analysis time by a factor of 3 with milk samples and by a factor of 2 with egg samples. Recovery of SAs in milk at the 5 ppb level ranged between 76 and 112% with relative standard deviations (RSDs) of <or=13%. Recovery of SAs in egg at the 50 ppb level ranged between 68 and 106% with RSDs of <or=12%. Estimated limits of quantification (S/N = 10) of the method were 1-6 ppb of SAs in whole milk and 5-13 ppb of SAs in eggs. Analyses of eggs from three layer chickens treated with sulfoquinoxaline revealed this antibacterial was still present at the 150 ppb level 1 week after withdrawal.