We assessed the ecotoxicological hazard potential of 42 pharmaceuticals from 22 therapeutic groups, including metabolites formed in humans. We treated each parent drug and its metabolites as a mixture of similarly acting compounds. If physicochemical or effect literature data were missing, we estimated these with quantitative structure-activity relationships (QSAR). Additionally, we estimated micropollutant removal efficiency of urine source separation using pharmaceutical information. On average, 50% of a parent drug was metabolized, and 70% was excreted with urine, albeit with large variations among drugs. Metabolism reduced the toxic potential of all but eight drugs. The subsequently modeled risk quotient was mostly below the threshold of one. However, ibuprofen and its metabolites in a mixture could pose an ecotoxicologal risk; and possibly also acetylsalicylic acid, bezafibrate, carbamazepine, diclofenac, fenofibrate, and paracetamol. Lipophilicity and sale quantities of parent drugs alone were insufficient to estimate their ecotoxicological risk. Urine separation could decrease the ecotoxicological risk of some, but not all drugs. The estimated risk quotients were equal in urine and feces, again with large variations among compounds. Because of scientific limitations of the model and inconsistent literature data the results are somewhat uncertain. However, this new approach allows first tier screening of single drugs, thus supporting decision-making.