Spatial and Temporal Tracking of Counterfeit Phosphodiesterase Type V Inhibitors Use Based on Wastewater Analysis

Phosphodiesterase type V inhibitors (PDE-5is) are widely used for the treatment of erectile dysfunction, and global demand for these pharmaceuticals continues to grow. However, the circulation of unlicensed and counterfeit PDE-5is poses serious public health risks. This study employed solid-phase extraction coupled with LC-MS/MS to analyze 116 influent wastewater samples collected in Dalian, China, in order to assess the temporal and spatial trends in the community-level use of counterfeit PDE-5is. Among the three target compounds, neither tadalafil nor vardenafil was detected in any sample. Sildenafil, however, was found in 94.5% of the samples, with concentrations ranging from below the limit of quantification (LOQ) to 75.4 ng/L. Its major metabolite, desmethylsildenafil, was detected in concentrations ranging from < LOQ to 107 ng/L. Sildenafil consumption steadily increased between 2017 and 2022 (40.8 to 87.8 mg/d/1000 inh). Notably, the estimated consumption based on wastewater data far exceeded local prescription sales, which accounted for only approximately 20% of the total use, with counterfeit sildenafil use estimated to exceed 100 kg/year in Dalian. This discrepancy indicates that the majority of sildenafil is obtained through over-the-counter sales or illegal channels. For spatial analysis, wastewater treatment plants were classified according to the characteristics of the populations they served. Sildenafil consumption was substantially higher in urban areas (70.4 mg/d/1000 inh) than in rural areas (25.4 mg/d/1000 inh), indicating more widespread use of counterfeit products in urban populations. Subpopulation analysis further revealed that college students (38.5 mg/d/1000 inh) and island residents (28.6 mg/d/1000 inh) had lower levels of use compared to the general population (85.1 mg/d/1000 inh). These results highlight the potential of wastewater-based drug surveillance in tracking consumption trends of nonprescribed and counterfeit pharmaceuticals, offering robust evidence to inform regulatory efforts and improve public risk perception.