Sulfonamides are antibiotic compounds widely used in the dairy industry. Their presence in diary milk poses a risk to public health and may also contribute to the spread of antibiotic resistance in bacteria. Sulfonamide residues in dairy milk were quantified by tandem mass spectrometry (MS/MS) using a novel ionization source based on laser diode thermal desorption-negative mode atmospheric pressure chemical ionization (LDTD-APCI(-)). Seven sulfonamides spiked in milk were extracted with acetonitrile, which yielded high recoveries (77.5-101.5%). Calibration curves in the matrix showed good linearity (0.9977 >or= R(2) >or= 0.9658) over the dynamic range (1.6-500 microg L(-1)), and limits of quantitation were between 2 and 14 microg L(-1), lower than or of the same magnitude as maximum residue criteria set by several regulatory agencies (10-100 ng L(-1)). In addition, the run time using the LDTD-MS/MS system was 30 s per sample, as compared to actual methods running from 7 to 84 min for the same sulfonamide residue compounds, which gave the method the high screening throughput capacity necessary for monitoring milk production.