Quantitative on-line preconcentration-liquid chromatography coupled with tandem mass spectrometry method for the determination of pharmaceutical compounds in water

•A multi-residues method has been developed for 40 pharmaceuticals determination with on-line preconcentration coupled to LC–MS/MS.•Matrix effects have been studied for tap and surface waters.•Low quantification limits have been validated for environmental analysis.•A survey showed the presence of 16 pharmaceuticals in Isle River and their absence in drinking water. One of the current environmental issues concerns the presence and fate of pharmaceuticals in water bodies as these compounds may represent a potential environmental problem. The characterization of pharmaceutical contamination requires powerful analytical method able to quantify these pollutants at very low concentration (few ngL−1). In this work, a multi-residue analytical methodology (on-line solid phase extraction-liquid chromatography–triple quadrupole mass spectrometry using positive and negative electrospray ionization) has been developed and validated for 40 multi-class pharmaceuticals and metabolites for tap and surface waters. This on-line SPE method was very convenient and efficient compared to classical off-line SPE method because of its shorter total run time including sample preparation and smaller sample volume (1mL vs up to 1L). The optimized method included several therapeutic classes as lipid regulators, antibiotics, beta-blockers, non-steroidal anti-inflammatories, antineoplastic, etc., with various physicochemical properties. Quantification has been achieved with the internal standards. The limits of detection are between 0.7 and 15ngL−1 for drinking waters and 2–15ngL−1 for surface waters. The inter-day precision values are below 20% for each studied level. The improvement and strength of the analytical method has been verified along a monitoring of these 40 pharmaceuticals in Isle River, a French stream located in the South West of France. During this survey, 16 pharmaceutical compounds have been detected.