Abstract
This study presents a comparison of three mass spectrometry-based analytical approaches-targeted tandem mass spectrometry (MS/MS), high-resolution full scan (HRFS), and data-independent acquisition (DIA)-for the quantification and screening of 74 pharmaceuticals across four environmental water matrices: tap water, river water, and influent and effluent wastewater. The methods were validated in terms of limits of quantification (LOQ), trueness, precision, and matrix effects. MS/MS exhibited the best overall performance, achieving the lowest LOQs (median 0.54 ng/L), highest trueness (median 101 %), and minimal matrix effects, confirming its suitability for routine regulatory monitoring. HRFS and DIA, while showing higher LOQs and variability, provided broader screening capabilities with acceptable trueness for 63 % and 81 % of compounds, respectively, and enabled retrospective data analysis. The methods were applied to real samples from the Živný Stream in the Czech Republic to determine pharmaceutical contamination downstream of a wastewater treatment plant (WWTP).