Exact mass measurements were performed on-line with high-performance liquid chromatography on a quadrupole mass spectrometer. Compounds with molecular weights from 98 to 797, mainly aromatic sulfonates and sulfonamides, were analyzed with electrospray ionization in positive or negative mode. Internal mass calibration compounds were continuously added after separation. A Gaussian fit of the mass errors of 808 individual measurements (concentrations of 1-10 mg/L, 20-200 ng absolute on column) resulted in a mean error of 0.1 mmu (0.45 ppm) and a standard deviation sigma of 1.5 mmu (5.4 ppm). The 99.7% confidence intervals (3sigma) were +/-4.5 mmu (+/-16.2 ppm) for single mass measurements. Averaging 10 measurements further reduced the errors to less than +/-1.5 mmu (+/-5 ppm). Isobaric interferences with ions resulting from the mass calibrants were avoided by the use of complementary mass calibrants. The results were verified (differences below +/-4.5 mmu) with a LC/ oa-TOFMS. Limited mass range chromatograms were used to enhance selectivity in the analysis of mixtures. The method was applied to determine the elemental composition of a potential dye metabolite detected in anaerobically treated textile wastewater.