Persistent pharmaceuticals and their transformation Products: From persistence mechanisms to AI-assisted integrated treatment for safe water reuse

This review examines the physicochemical mechanisms governing pharmaceutical persistence, the formation of transformation products (TPs), and the effectiveness and limitations of conventional and advanced treatment technologies for water reuse, focusing on carbamazepine, diclofenac, iodinated contrast media, metformin, and selected antibiotics, which persist through wastewater treatment. The review follows one chain of reasoning: persistence drivers determine which TPs form, which compartments and exposure pathways are reached, and which treatment barriers can act. Conventional activated sludge often provides incomplete removal, whereas integrated trains combining biological processes, adsorption, ozonation, UV/H 2 O 2 , membranes, and other advanced oxidation technologies can improve control, although energy demand, membrane fouling, residuals, and TP formation remain constraints. Pilot- and full-scale studies report average abatement of about 80% or more with ozonation or activated carbon, but behavior differs among compounds, and evidence for complete multi-barrier trains is limited. Unlike reviews addressing occurrence, individual technologies, or TPs separately, this review links the drivers of persistence to the selection and sequencing of treatment barriers, and extends the assessment to groundwater migration, soil–plant and food-chain transfer, and antimicrobial-resistance pathways within a common water-reuse framework. This supports adaptive treatment design targeting parent compounds, TPs, and cross-compartment risks. HRMS, non-target screening, and AI/ML-assisted optimization support adaptive monitoring and control. However, identifying a TP does not demonstrate risk, so effect-based methods are needed, and AI/ML applications are mainly predictive and validated on small datasets. Safe and sustainable water reuse likely requires multi-barrier treatment, source control, continuous monitoring, TP assessment, and integrated risk management.