Journal of Pharmaceutical and Biomedical Analysis Open · Published 2026-05-01 · DOI 10.1016/j.jpbao.2026.100112
Opioid-like designer drugs are a rapidly evolving subset of new psychoactive substances (NPS), potent synthetic opioids that increasingly challenge established toxicological and forensic workflows. Beyond fentanyl analogues, laboratories are now confronted with multiple chemotypes, including nitazenes and U-series opioids, which commonly circulate as closely related structural variants, isomers and mixtures. Their high potency and low administered doses often result in trace-level concentrations in biological matrices, complicating both detection and confirmation. Routine immunoassays and static targeted analytical procedures may be inadequate when cross-reactivity is limited or when emerging compounds are not included in predefined libraries. Confirmatory analysis is further hindered by shared fragmentation patterns, limited availability of reference standards and incomplete metabolic information. This review summarises practical analytical approaches aimed at maintaining analytical adaptability without compromising routine feasibility, including tiered screening strategies, robust HPLC-MS/MS confirmation criteria, and the use of high-resolution mass spectrometry (HRMS) for suspect screening and retrospective data interrogation. Attention is given to producing the desired level of structural specificity and analytical reliability, supporting reliable interpretation in clinical, forensic and public health settings.
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