Synthetic cannabinoids in hair: a review of recent findings and analytical methods by LC-MS/MS

Synthetic cannabinoids (SCs) represent a prominent class of new psychoactive substances (NPS), defined as substances of abuse that pose a significant public health threat. SCs are characterized by their structural diversity, high potency, and associated health risks. Their continuous emergence on the illicit drug market - driven by ongoing structural modifications - poses significant challenges for analytical detection, regulation, and toxicological evaluation. Hair analysis has proven to be a valuable biological matrix in forensic toxicology, offering an extended detection window and the ability to reflect chronic exposure.

This critical review focused on the application of liquid chromatography coupled to mass spectrometry (LC-MS/MS) for the determination of SCs in hair. The most important steps in hair sample preparation - collection, segmentation, decontamination, pulverization, and extraction - are evaluated in depth. The advantages and limitations of both low-resolution and high-resolution mass spectrometry are discussed. Comprehensive tables summarize the main methodological parameters related to sample preparation and instrumental conditions.

Covering studies published between 2013 and 2025, this review presents an in-depth assessment of LC-MS/MS methodologies for SCs determination in hair, from sample preparation to instrumental optimization. It also provided an updated overview of SCs, considering nomenclature and toxicological effects. The findings underscore the pressing need for continued methodological advancements to improve SCs determination, supporting more accurate toxicological interpretations and providing new insights for forensic field.