A sensitive and reliable method based on solid-liquid extraction (SLE) using McIlvaine-Na2EDTA buffer (pH = 4.5)-methanol and solid-phase extraction (SPE) clean up prior to ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) was applied to determine 47 organic contaminants in fish, soil and sediments. The SPE procedure to clean-up the extracts was also used as extraction method to determine these compounds in water. Recoveries ranged from 38 to 104% for all matrices with RSDs < 30%. Limits of Quantification for the target compounds were in the range of 10–50 ng/g for soil, 2–40 ng/g for sediment, 5–30 ng/g for fish and 0.3–26 ng/L for water. Furthermore, the proposed method was compared to QuEChERS (widely used for environmental matrices) that involves extraction with buffered acetonitrile (pH 5.5) and dispersive SPE clean-up. The results obtained (recoveries>50% for 36 compounds in front of 9, matrix effect < 20% for 31 compounds against 21, and LOQs <25 ng g−1 for 38 compounds against 22) indicates that the proposed method is more efficient than QuEChERS, The method was applied to monitoring these compounds along the Turia River. In river waters, Paracetamol (175 ng L−1), ibuprofen (153 ng L−1) and bisphenol A (41 ng L−1) were the compounds most frequently detected while in sediments were vildagliptin (7 ng g−1) and metoprolol (31 ng g−1) and in fish, bisphenol A (33 ng g−1) or sulfamethoxazole (13 ng g−1).