Estimating the consumption of prescription opioids through wastewater analysis: The patterns of use in Italy

Prescription opioids have recently experienced a diversion of use in several countries causing a huge number of overdoses due to their high potency. The aim of this study was to develop a wastewater-based epidemiology (WBE) approach to assess the use of prescription opioids and evaluate the compliance to prescriptions to highlight the potential misuse of these substances in Italy. The most prescribed opioids have been selected and validated as WBE biomarkers and a nation-wide study has been conducted over a three-year period (2020-2022). Wastewater (WW) samples were collected as 24-hour composite samples in eight Italian cities and parent substances or metabolites were quantified using validated analytical methods based on liquid chromatography - tandem mass spectrometry (LC-MS/MS). Daily loads have been normalized to therapeutic doses to obtain a real figure of use that showed higher use of tapentadol and morphine compared to oxycodone and fentanyl. Back-calculation of consumption estimates was done by using the most reliable WBE biomarkers and were compared with prescription data. Spatial and temporal differences were found and highlighted a lower use in the south compared to the north and the center of Italy. Data comparison with prescriptions gave results in the same range indicating that the use of these substances in Italy seems to be predominantly from prescription for therapeutic purposes. This study highlighted the suitability of WBE to investigate the potential non-medical use of prescription pharmaceuticals in a population, providing relevant information for supporting public health emergencies and policies.