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The occurrence of pharmaceuticals in the aquatic environment was mainly neglected in previous decades, although enormous quantities are used world-wide. In our laboratory, we therefore developed analytical procedures for a total of 84 drug-related analytes, enabling the simultaneous determination of polar drug residues belonging to different medicinal classes, such as lipid regulators, antibiotics, antiepileptics, anti-inflammatory agents, and estrogens in raw sewage, sewage treatment plant (STP) effluents, and river and drinking water. In a search for target analytes, 36 of 55 pharmaceuticals and 5 of 9 metabolites were quantified in at least one STP effluent. The highest concentration of drug residues were measured for the antiepileptic carbamazepine, with a maximum of 6.3 μg/L; X-ray contrast media were found in concentrations as high as 15 μg/L (iopamidol). In 40 German rivers and streams, 31 pharmaceuticals and five metabolites were quantified in at least one sample. Highest median values were detected for bezafibrate (0.35 μg/L) and carbamazepine (0.25 μg/L). Frequently, in small rivers and streams, much higher concentrations were detected than in higher-order rivers such as the Rhine or Main. Even in groundwater samples taken close to stream banks, sometimes relatively high concentrations of pharmaceuticals (e.g., up to 1.1 μg/L for carbamazepine) were detected. Hence, in the aquatic environment, drug residues are ubiquitously distributed. In distinct contrast, for drinking water only 10 of 69 target pharmaceuticals were found - always in the lower ng/L-range and in very few samples.