Using HPLC method with DAD detection for the simultaneous determination of 15 pharmaceuticals from different therapeutic groups in surface water and wastewater was proposed. The determined drugs included the analgesic non-steroidal anti-inflammatory drugs (NSAIDs) paracetamol (PAR), metamizole (MTZ), aspirin (ASP), salicylic acid (SAL), ibuprofen (IBU), ketoprofen (KET), diclofenac (DIC), and naproxen (NAP); the corticosteroids dexamethasone (DEX) and prednisolone (PRE); the β-blockers carvedilol (CAR), metoprolol (MET), propranolol (PRO), and sotalol (SOT); and the anticonvulsant carbamazepine (CBM). Three solid-phase extraction (SPE) columns were examined for the pre-concentration of water samples: the Oasis HLB, NEXUS and Bond Elut ENV. The concentration level for which each method was validated in spiked water samples was 0.2 μg/L. The Oasis HLB column yielded the best recovery efficiency. Different HPLC columns were examined to achieve the best separations with the shortest possible time. The best column, C30 and was used for the determination of drugs from water samples.. The proposed method was applied to the analysis of water samples, mostly from rivers, and can be used for screening as a rapid and low-cost analytical tool. However, to confirm the positive findings MS techniques should be applied.