The potential of solid-phase extraction coupled on-line to liquid chromatography/electrospray tandem mass spectrometry (SPE-LC-ESI-MS/MS) has been investigated in this paper for the efficient sensitive quantification and confirmation of 16 antibiotics in water. The list of targeted analytes included 10 quinolones (oxolinic acid (OXO), nalidixic acid (NAL), flumequine (FLU), marbofloxacine (MAR), ofloxacine (OFLO), enrofloxacine (ENR), pefloxacine (PEF), ciprofloxacine (CIP), pipemidic acid (PIPE), norfloxacine (NOR)) and 6 penicillins (penicillin G (PEN), oxacillin (OXA), dicloxacillin (DIC), piperacillin (PIP), cloxacillin (CLO) and ampicillin (AMP)) that were determined in ground and surface water. The procedure is based on the injection of 9.8 mL of sample into the SPE-LC-MS/MS system and the measurement of antibiotics by selected reaction monitoring mode, using a triple quadrupole analyser. The method has been validated at realistic low concentrations that might be present in environmental water, i.e. 10 and 100 ng L(-1), obtaining recoveries between 74% and 123% with relative standard deviation lower than 14%. Matrix effects were not relevant in most of cases, except for ampicillin in surface water, where notable signal suppression was observed. The limits of detection were as low as 0.4-4.3 ng L(-1). The method developed allows the rapid screening and quantification of all the analytes selected by acquiring one MS/MS transition (normally the most sensitive) for each compound. It was applied to a number of actual surface and groundwater samples with several compounds being detected, mainly quinolones, at low ng L(-1) levels. Special attention was given to the confirmation of compounds detected in water due to the difficulties of obtaining confident confirmation at low ng L(-1). This matter has been of growing concern in the last few years as reflected by recent papers and correspondence. The acquisition of several MS/MS transitions for each compound detected in a second independent analysis allowed the unequivocal confirmation of identity, avoiding reporting false-positives. Finally, the potential of QTOF instruments to confirm positive samples has also been evaluated and compared with triple quadrupole analysers.