The detection and quantitation of pharmaceutical compounds (PCs) in different environmental matrices is still a challenge, due to their extremely low (ng-μg) concentrations and the lack of rapid and sensitive analytical techniques. A number of techniques, such as enzyme-linked immunosorbent assay (ELISA), chromatography, electrophoresis, and electrochemical methods have been explored. These methods are limited by their poor sensitivity. In this study, a hyphenated liquid chromatography-mass spectrometric (LC-MS) method was developed, validated, and tested for the detection and quantification of seven active pharmaceutical compounds, with solid-phase extraction for analytes recovery and separation of interference from the aqueous matrix. The sensitivity achieved for the method allowed for LODs (μg/L) of 0.0439, 0.0684, 0.1219, 0.0710, 0.1129, 0.0447, 0.0837 and LOQs (μg/L) of 0.1462, 0.2281, 0.4065, 0.2367, 0.3763, 0.1492, 0.2792, for lamivudine, acetaminophen, vancomycin, ciprofloxacin, sulfamethoxazole, diclofenac, and ivermectin, respectively, within a linear range of 0.01–0.1 μg/mL. Other ICH validation parameters are also discussed. The different PCs were positive in 61 % of the tested surface waters, with diclofenac present only in two of the sampling points. The concentrations at which they occurred were variable and ranged between ND and 398.98 μg/L.