An automated flow analysis-solid phase extraction (FA-SPE) system and methodology of ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis were developed for the determination of selected antiviral drugs (acyclovir, amantadine, rimantadine, and oseltamivir) in water samples. The proposed FA-SPE approach enables the integration of various extraction stages and elimination of the sample evaporation step and offers individual customisation of SPE parameters, inter alia sample, and eluate flow rate and volume. Using the developed FA-SPE procedure, e.g. a 100-fold preconcentration of the target analytes in 1 h was achieved. A method for chromatographic analysis was also developed to determine the selected antiviral drugs in combination with the use of the FA-SPE system. The developed FA-SPE UHPLC-MS/MS method was validated including the determination of linearity of analytical graphs, limits of detection (5.5-99.9 pg mL-1) and quantification (18.3-329.8 pg mL-1), intra-day (1.8-8.3%) and inter-day (3.0-9.2%) precision, recovery (95.6-105.3%), and matrix effects (- 12.9 to 13.2%). The proposed method was successfully applied to analyse tap, drinking, and river water samples, revealing the presence of amantadine at a concentration of 40.1 pg mL-1 in one sample. The environmental impact of the developed FA-SPE sample preparation procedure was also assessed using the AGREEprep metric tool and compared with five other literature methods, achieving the most sustainable outcome.

Department of Analytical Chemistry Faculty of Chemistry Jagiellonian University Gronostajowa 2 30 387 Kraków Poland

Department of Analytical Chemistry Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 8 500 03 Hradec Králové Czech Republic

Department of Environmental Chemistry Faculty of Chemistry Jagiellonian University Gronostajowa 2 30 387 Kraków Poland

Doctoral School of Exact and Natural Sciences Jagiellonian University Łojasiewicza 11 30 348 Kraków Poland

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