Pharmaceutical mixtures in urban wastewater: integrating occurrence and ecotoxicological potency for prioritization, informed by co-occurrence structure.

Pharmaceutical mixtures are pervasive contaminants in urban wastewater, yet prioritization strategies still rely predominantly on single-substance approaches that neglect mixture structure and the population scale of emission sources. Here, we propose the Index of Community Exposure to Pharmaceuticals in Effluents (iCEPE), a composite prioritization framework integrating occurrence frequency, population exposure, ecotoxicological potency, and pharmaceutical co-occurrence networks. The framework was applied to 61 sampling events collected across six wastewater monitoring units (five WWTPs and one hospital effluent) serving approximately 2.9 million inhabitants in Curitiba, southern Brazil. Among 14 retained pharmaceuticals, 57% were classified as high priority, with diclofenac, ethinylestradiol, and sulfamethoxazole consistently ranking highest due to distinct combinations of ubiquity, toxicity, and network connectivity. The prioritization substantially diverged from frequency-based ranking alone (ρ = 0.824), demonstrating that ecotoxicological potency strongly influences environmental priority assignment. Co-occurrence analysis revealed a near-saturated pharmaceutical network (density = 0.95), indicating systemic metropolitan-scale co-exposure rather than localized contamination patterns. Robustness analyses across alternative weighting schemes, model specifications, and population formulations showed high ranking stability (ρ > 0.938), supporting the consistency of the prioritization framework. The results indicate that pharmaceutical contamination in the Curitiba metropolitan wastewater system is structurally widespread and characterized by widely co-occurring pharmaceuticals of high monitoring priority. As a relative prioritization framework, the iCEPE ranks compounds for monitoring and management priority and does not quantify ecological risk or population exposure. Overall, the iCEPE framework provides a transferable tool for translating routine wastewater monitoring data into environmentally relevant pharmaceutical prioritization for urban water management and surveillance programs.