Drugs in the environment and its potential toxic effects are recognised problems in the environmental chemistry area. Drugs can be biodegraded in the wastewater treatment plants (WWTP) as a result of microbial processes. However, the degradation capability of the microbial community of an activated sludge could change over time. In OECD ready biodegradability tests (RBTs), the use of a reference compound that is usually easily and fast degraded is recommended in order to ensure that the microbial community in the test system is active. However, the biodegradability of most drugs is poor and slow compared with the classical proposed reference compounds. In this work, fluoxetine (among other drug candidates tested) was suggested as a consistent reference compound to control the activity of activated sludges in drug biodegradation studies. To characterize its biodegradability features, fluoxetine was assayed in OECD RBTs-recommended conditions. Experiments were performed using activated sludges taken at different dates from a local WWTP, different storage times, and by three different operators (intermediate precision study). A fluoxetine-biodegradation acceptance criterionthat could be connected to data from other drugs or comparison studies (different procedures, conditions, activated sludges) was proposed.