An analytical procedure for the determination of 10 drugs belonging to three different therapeutic groups was analysed. Several compounds were investigated which comprise of beta-blockers: sotalol (SOT), metoprolol (MET), propranolol (PRO), carvedilol (CAR); corticosteroids: prednisolone (PRE), dexamethasone (DEX); analgesic, non-steroidal anti-inflammatory (NSAID): paracetamol (PAR), metamizole (MTZ), aspirin (ASP) and ketoprofen (KET). Reversed-phase liquid chromatography with gradient elution, fluorescence (FL) and diode array detectors (DAD) was applied for the selective investigation of the drugs. Three solvents were used as the mobile phase: methanol, 0.05% trifluoroacetic acid (TFA) in water and acetonitrile. The solid phase extraction (SPE) method using the Oasis HLB column was proposed for the preconcentration step. The recovery level for most of the drugs was above 80%. The low values of limits of detection (LOD) for PAR, SOT, MTZ, MET, SAL, PRO, PRE, CAR, DEX and KET were achieved: 106 ng L−1, 1,048 ng L−1, 2.48 ng L−1, 2.17 ng L−1, 16.5 ng L−1, 1.10 ng L−1, 160 ng L−1, 6.62 ng L−1, 76.5 ng L−1 and 45.2 ng L−1, respectively. The suggested method was used for the determination of drugs in spiked surface water.