Molecular Imprinting Polymer (MIP)-Based Technologies and Applications for the Detection and Identification of Psychoactive Substances
Kumsal Kocadal, Nunzianda Frascione, Vincenzo Abbate, Dilek BattalMolecularly imprinted polymers (MIPs) are synthetic receptors in which a template-shaped cavity, formed by polymerising functional monomers around the target and then removing it, confers preferential rebinding of that target. Their chemical and thermal robustness, low unit cost, straightforward preparation and reusability make them attractive recognition elements for psychoactive substance analysis, a field constrained by sample throughput, cost and the need for field-deployable measurement. This review is restricted to small-molecule targets and distinguishes four groups whose forensic and regulatory contexts differ: classical controlled drugs, novel psychoactive substances (NPSs), psychoactive medicinal products, and performance-enhancing agents encountered in the same laboratory workflows. We summarise (i) the imprinting formats and computational pre-screening strategies relevant to these targets and (ii) their implementation in electrochemical, optical and piezoelectric sensors, in chromatographic and spectroscopic sample preparation, and in microfluidic platforms. Reported figures of merit are compiled on a common molar basis to permit direct comparison across platforms. We then assess the factors that currently govern forensic and clinical deployment: cross-reactivity towards close structural analogues, which for imprinted receptors typically remains well above the one-to-two per cent level and makes them class-selective rather than compound-specific; residual template bleeding; electrode fouling in undiluted biological fluids; and the reproducibility and scale-up of imprinting. On this evidence, the productive role of MIPs in clinical and forensic toxicology is as class-selective extraction sorbents and rapid presumptive screening devices upstream of chromatographic confirmation, rather than as replacements for it.