Combination of stable isotope ratio data and chromatographic impurity signatures as a comprehensive concept for the profiling of highly prevalent synthetic cannabinoids and their precursors

Sascha Münster-Müller; Nicole Scheid; Ralf Zimmermann; Michael Pütz

doi:10.1016/j.aca.2020.01.029

Combination of stable isotope ratio data and chromatographic impurity signatures as a comprehensive concept for the profiling of highly prevalent synthetic cannabinoids and their precursors

Anal Chim Acta. 2020 Apr 29:1108:129-141. doi: 10.1016/j.aca.2020.01.029. Epub 2020 Jan 16.

Authors

Sascha Münster-Müller¹, Nicole Scheid², Ralf Zimmermann³, Michael Pütz²

Affiliations

¹ Federal Criminal Police Office, Forensic Science Institute, Äppelallee 45, 65203, Wiesbaden, Germany; Joint Mass Spectrometry Centre, Institute of Chemistry, Chair of Analytical Chemistry, University of Rostock, 18057, Rostock, Germany. Electronic address: Sascha.muenstermueller@googlemail.com.
² Federal Criminal Police Office, Forensic Science Institute, Äppelallee 45, 65203, Wiesbaden, Germany.
³ Joint Mass Spectrometry Centre, Institute of Chemistry, Chair of Analytical Chemistry, University of Rostock, 18057, Rostock, Germany; Joint Mass Spectrometry Centre, Cooperation Group "Comprehensive Molecular Analytics", Helmholtz Zentrum Muenchen, 85764, Neuherberg, Germany.

PMID: 32222234
DOI: 10.1016/j.aca.2020.01.029

Abstract

In this study, we utilized elemental analyser (EA) and gas-chromatography (GC) isotope ratio mass spectrometry (IRMS) and ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) in a comprehensive profiling approach assessing the chromatographic impurity signatures and δ¹³C and δ¹⁵N isotope ratios of synthetic cannabinoids from police seizures and internet test purchases. Main target of this study was the highly prevalent synthetic cannabinoid MDMB-CHMICA (methyl (2S)-2-([1-(cyclohexylmethyl)-1H-indol-3-yl]formamido)-3,3-dimethylbutaoate). Overall, 61 powder and 118 herbal blend (also called "Spice-Products") samples were analysed using both analytical techniques and evaluated in a joint model to link samples from a common source. As a key finding, three agglomerates of Spice-product samples with similar dates of purchase were identified in the IRMS data, possibly representing larger shipments of MDMB-CHMICA, each produced with the same precursor material, successively delivered to the European market. The three agglomerates were refined into multiple sub-clusters based on the impurity profiling data, each representing an individual synthesis batch. One of the agglomerates identified in the IRMS data was found to consist two groups of four sub-clusters, respectively, with majorly different impurity profiles, demonstrating the necessity for both analytical techniques to extract the maximum amount of information from a limited sample pool. Additionally, 31 samples containing the recently surfaced synthetic cannabinoid Cumyl-PeGaClone (5-pentyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one) were analysed for their and δ¹³C and δ¹⁵N isotope ratios to put the isotopic data recorded for MDMB-CHMNICA in a more global perspective. Three building blocks of precursor chemicals (indole, tert-leucine, cumylamine) potentially used for the synthesis of the two named synthetic cannabinoids were acquired from different global vendors and measured for their δ¹³C and δ¹⁵N isotope ratios to better understand variations in the isotopic composition of the synthetic cannabinoids and to trace their origin.

Keywords: Cumyl-PeGaClone; Impurity profiling; Isotope ratio mass spectrometry; MDMB-CHMICA; New psychoactive substances.