Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F‐MDMB‐PICA

Abstract

Abstract5F‐MDMB‐PICA, an indole‐type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F‐MDMB‐PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F‐MDMB‐PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high‐resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography–tandem mass spectrometry and ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F‐MDMB‐PICA uptake.