Microplastics as vectors and reservoirs of pharmaceuticals and drugs of abuse: experimental evidence, mechanistic predictions and analytical challenges

Microplastics (MPs) are increasingly investigated as particulate phases capable of interacting with emerging organic contaminants in aquatic environments. This review critically evaluates experimental evidence for pharmaceutical-MP interactions and distinguishes it from mechanistic extrapolation for drugs of abuse, for which direct sorption data remain largely unavailable. Environmental occurrence data for drugs of abuse are used to establish environmental relevance and prioritize target analytes rather than as evidence of sorption onto MPs. Particular emphasis is placed on the role of physicochemical speciation, including pH-dependent lipophilicity (logD), ionization equilibria, and the evolution of polymer surfaces, in governing contaminant-particle interactions. Experimental evidence indicates that sorption onto MPs cannot be described solely by hydrophobic partitioning (logK ow ), but involves coupled mechanisms, including electrostatic interactions, aging-induced surface oxidation, and biofilm-mediated processes. For drugs of abuse and new psychoactive substances, current knowledge is mainly limited to environmental occurrence and physicochemical properties, which can support testable mechanistic hypotheses but not quantitative predictions. Predictive models remain poorly constrained, particularly because of the scarcity of pH-dependent plastic-water partition coefficients (K pw ) for ionizable compounds. From an analytical perspective, the integration of microplastic sampling with LC-HRMS-based workflows introduces significant methodological challenges. Sampling artifacts, extraction-induced redistribution, matrix effects in electrospray ionization, adduct formation, in-source fragmentation, and variability in identification confidence levels in non-target analysis directly affect data interpretation. The lack of harmonized QA/QC protocols further limits comparability across studies. Progress toward a dynamic and quantitative framework requires controlled sorption and desorption experiments with HRMS, standardized reporting, and models that account for chemical speciation. This combined approach is essential for robust exposure assessment and for testing mechanistic predictions for ionizable contaminants, particularly drugs of abuse.