High-performance liquid chromatography coupled with positive-ion electrospray ionisation tandem mass spectrometry was used for the determination and confirmation of 13 sulphonamide drugs in environmental water samples in the low ng/L-range. Enrichment with concentration factors of 130–670 was performed by solid phase extraction, achieving recoveries of 50 to 90%. After gradient elution HPLC, detection and quantification was performed using selected reaction monitoring (SRM) with limits of detection between 0.2 and 3.7 μg/L. Confirmation was obtained by either SRM transitions of collision induced dissociation reactions or daughter ion mass spectra. Primary and secondary effluents of municipal waste water treatment plants and different surface waters were examined. The compounds sulphamethoxazole and sulphadiazine were detected and confirmed with concentrations ranging between 30–2000 ng/L and 10–100 ng/L, respectively. The compound sulphamethizole was detected in low amounts but could not be positively confirmed.