This paper describes the development and validation of a simple analytical method using solid-phase extraction followed by a high-performance liquid chromatography with diode array detection (HPLC-DAD) analysis. Target compounds included six pharmaceuticals (carbamazepine, diazepam, fluoxetine, propranolol, sulfamethoxazole, and trimethoprim) and the active metabolite of fenofibrate (fenofibric acid). Briefly, this method consisted of the preconcentration of water samples (2 L) on 500 mg Oasis HLB cartridges and HPLC analysis using a RP-₁₈ analytical column in a gradient mode with a flow rate of 1 mL/min. The validation parameters revealed that this method was highly specific for all assayed compounds (> 99%), and the linearity of the calibration curves always showed a correlation higher than 0.99. The detection limits were in the ng/L level, and recovery rates were > 70% for most of the target compounds. Analysis of samples from polluted areas of the Douro River estuary indicated that propranolol and carbamazepine are present in concentrations ranging from 22.0 to 54.0 ng/L and 21.3 to 32.7 ng/L, respectively. Thus, it is concluded that this method can be successfully applied for screening pharmaceuticals in polluted estuarine areas.