Fast and comprehensive multi-residue analysis of a broad range of human and veterinary pharmaceuticals and some of their metabolites in surface and treated waters by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem

The present work describes the development of an analytical method, based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UPLC-QqLIT) for the determination of 81 pharmaceutical residues, covering various therapeutic groups, and some of their main metabolites, in surface and treated waters (influent and effluent wastewaters, river, reservoir, sea and drinking water). For unequivocal identification and confirmation, two selected reaction monitoring (SRM) transitions per compound are monitored. Quantification is performed by the internal standard approach, indispensable to correct matrix effects. Moreover, to obtain an extra tool for confirmation of positive findings, an information dependent acquisition (IDA) experiment was performed, with SRM as survey scan and an enhanced product ion (EPI) scan as dependent scan. Compound identification was carried out by library search, matching the EPI spectra achieved at one fixed collision energy with those present in a library. The main advantages of the method are automation and speed-up of sample preparation by the reduction of extraction volumes for some matrices, the fast separation of a big number of pharmaceuticals, its high sensitivity (limits of detection in the low ng/L range), selectivity, due to the use of tandem mass spectrometry, reliability since a significant number of isotopically labeled compounds are used as internal standards for quantification and finally, the analysis of tap, reservoir and sea waters, since information about occurrence of pharmaceuticals in these matrices is still sparse. As part of the validation procedure, the method developed was applied to the analysis of pharmaceutical residues in waste and surface waters from different sites in Catalonia (North East of Spain).

► Simultaneous determination of 81 pharmaceuticals and some metabolites.
► Speed-up of sample preparation is achieved.
► High sample throughput and high sensitivity are achieved.
► IDA and library searching is a powerful tool for the confirmation of positive findings.
► Levels for carbamazepine metabolites are more prominent than the parent compound.