The development of a method to confirm the presence of sulfonamide residues in kidney tissues at levels at or above the maximum residue limit (MRL, 100 ng g^–1 total sulfonamide) using a tandem mass spectrometer [i.e., mass spectrometry–mass spectrometry (MS–MS)] interfaced to a high-performance liquid chromatograph is described. Although sulfonamides can be determined using a single quadrupole mass spectrometer with pseudo-MS–MS, advantages in interfacing to a tandem mass spectrometer are demonstrated.