Pharmaceutical residues have become tightly controlled environmental contaminants in recent years, due to their increasing concentration in environmental components. This is mainly caused by their high level of production and everyday consumption. Therefore there is a need to apply new and sufficiently sensitive analytical methods, which can detect the presence of these contaminants even in very low concentrations. This study is focused on the application of a reliable analytical method for the analysis of 10 selected drug residues, mainly from the group of non-steroidal anti-inflammatory drugs (salicylic acid, acetylsalicylic acid, clofibric acid, ibuprofen, acetaminophen, caffeine, naproxen, mefenamic acid, ketoprofen, and dicofenac), in wastewaters and surface waters. This analytical method is based on solid phase extraction, derivatization by N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) and finally analysis by comprehensive two-dimensional gas chromatography with Time-of-Flight mass spectrometric detection (GC×GC- TOF MS). Detection limits ranged from 0.18 to 5 ng/L depending on the compound and selected matrix. The method was successfully applied for detection of the presence of selected pharmaceuticals in the Svratka River and in wastewater from the wastewater treatment plant in Brno-Modrice, Czech Republic. The concentration of pharmaceuticals varied from one to several hundreds of ng/L in surface water and from one to several tens of μg/L in wastewater. Due to their increasing level in environmental components. Therefore there is a high degree of production and everyday consumption. can detect the presence of these contaminants even in very low concentrations. This study is focused on the application of a reliable analytical method for the analysis of 10 selected drug residues, mainly from the group of non-steroidal anti-inflammatory drugs (salicylic acid, acetylsalicylic acid, clofibric acid, ibuprofen, acetaminophen, caffeine, naproxen, mefenamic acid, ketoprofen, and dicofenac, in wastewaters and surface waters. This analytical method is based on solid phase extraction, derivatization by N-methyl- trifluoroacetamide (MSTFA) and finally analysis by comprehensive two-dimensional gas chromatography with Time-of-F Light mass spectrometric detection (GC × GC-TOF MS). Detection limits ranged from 0.18 to 5 ng / L depending on the compound and selected matrix. The method was successfully applied for detection of the presence of selected pharmaceuticals in the Svratka River and in wastewater from the wastewater treatment plant in Brno-Modrice, Czech Republic. The concentration of pharmaceuticals varied from one to several hundreds of ng / L in surface water and from one to several tens of μg / L in wastewater.