Simultaneous Quantification of 3 Synthetic Cannabinoids and 4 of Their Metabolites in Human Urine Samples and Seized Samples by LC‐MS/MS

The rapid emergence of synthetic cannabinoids (SCs) presents significant challenges for forensic toxicology, requiring sensitive and reliable analytical methods for both seized materials and biological specimens. This study reports the development and validation of an LC–MS/MS method for the simultaneous qualitative and quantitative determination of SCs in illicit products and human urine. The method allows concurrent detection of three parent SCs ‐MDMB‐4en‐PINACA, 4F‐MDMB‐BUTICA, and 5F‐MDMB‐PICA—and four major metabolites, including MDMB‐4en‐PINACA butanoic acid, 4F‐MDMB‐BUTICA N‐(4‐hydroxybutyl), 4F‐MDMB‐BUTICA butanoic acid, and 5F‐MDMB‐PICA butanoic acid. The limits of detection ranged from 0.03 to 0.2 ng/mL, with a lower limit of quantification of 1.0 ng/mL, enabling the identification of low‐level exposure. Excellent linearity was achieved across the calibration ranges ( R 2 > 0.998). Application of the method to seized products in Vietnam confirmed the presence of the three target SCs in multiple samples. Analysis of urine specimens from users demonstrated consistent detection of parent compounds and characteristic metabolites, with metabolite concentrations reaching up to 243.8 ng/mL, supporting recent SC consumption. The developed method is well suited for forensic toxicology applications, providing a robust approach for confirming synthetic cannabinoid exposure in legal, clinical, and investigative contexts.