Synthetic cannabinoids: a critical review of challenges and advances in biological sample preparation

Synthetic cannabinoids (SCs) are the largest and most diverse class of new psychoactive substances (NPS) and continue to account for the highest number of newly emerging compounds on the market. The vast chemical diversity, complex metabolism, low concentrations in biological samples, and rapid emergence of new NPS make it challenging for forensic methods to keep pace. In this scoping review, the recent advances and challenges of the SCs analysis in biological samples are described. Published studies from January 2018 to August 2025 were searched in 8 databases, and after screening and exclusions, the selected 33 articles had their data tabulated, summarized, and analyzed. The main characteristics of the groups of SCs analyzed and the potential use of each biological sample were described, indicating gaps in the literature that still need to be explored. Challenges regarding the use of reference standards for SCs and their metabolites are discussed. Well-established and emerging sample preparation protocols, along with chromatographic separation techniques, are reviewed with a focus on their advantages, limitations, and challenges. The application of Green Analytical Chemistry (GAC) principles and White Analytical Chemistry (WAC) within these approaches is also explored. Finally, the review addresses future directions, emerging challenges, and current trends in the analysis of synthetic cannabinoids.