The use of pharmaceuticals in livestock production is a potential source of surface water, groundwater and soil contamination. Possible impacts of antibiotics on the environment include toxicity and the emergence of antibiotic resistance. Monitoring programs are required to record the presence of these substances in the environment. A rapid, versatile and selective multi-method was developed and validated for screening 43 pharmaceutical and fungicides compounds, in surface and groundwater, in one single full-scan MS method, using benchtop U-HPLC-Exactive Orbitrap MS at 50,000 (FWHM) resolution. Detection was based on calculated exact masses and on retention time. Sample volume, pH conditions and solid-phase extraction (SPE) sample clean-up conditions were optimized. In the final method, 74 % of the compounds had recoveries higher than 80 %, 15 % of the compounds had recoveries between 60 % and 80 %, and 7 % of the compounds had recoveries between 40 % and 50 %. One of the compounds (itraconazole) had a recovery lower than 10 % and nystatin was not detected. The level of detection was 10 ng L-1 for 61 % of the compounds, 50 ng L-1 for 32 % and 100 ng L-1 for 5%. In-house validation, based on EU guidelines, proves that the detection capability CC beta is lower than 10 ng L-1 (for beta error 5 %) for 37 % of the compounds, lower than 50 ng L-1 for 35 % of the compounds and lower than 100 ng L-1 for 14 % of compounds. This study demonstrates that the ultra-high resolution and reliable mass accuracy of Exactive Orbitrap MS permits the detection of pharmaceutical residues in a concentration range of 10-100 ng L-1, applying a post target screening approach, in the multi-method conditions.