Analytical Characterization of 3-MeO-PCP and 3-MMC in Seized Products and Biosamples: The Role of LC-HRAM-Orbitrap-MS and Solid Deposition GC-FTIR

Giampietro Frison; Flavio Zancanaro; Samuela Frasson; Laura Quadretti; Michele Agnati; Francesca Vlassich; Giuseppe Gagliardi; Tania Maria Grazia Salerno; Paola Donato; Luigi Mondello

doi:10.3389/fchem.2020.618339

Analytical Characterization of 3-MeO-PCP and 3-MMC in Seized Products and Biosamples: The Role of LC-HRAM-Orbitrap-MS and Solid Deposition GC-FTIR

Front Chem. 2021 Feb 8:8:618339. doi: 10.3389/fchem.2020.618339. eCollection 2020.

Authors

Affiliations

¹ Laboratory of Environmental Hygiene and Forensic Toxicology, DMPO Department, AULSS 3, Venice, Italy.
² Emergency Department Unit, Madonna della Salute Hospital, AULSS 5, Porto Viro (Rovigo), Italy.
³ Intensive Care Unit, Madonna della Salute Hospital, AULSS 5, Porto Viro (Rovigo), Italy.
⁴ Department of Anesthesiology and Intensive Care, AULSS 5, Porto Viro (Rovigo), Italy.
⁵ BeSep S.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
⁶ Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy.
⁷ Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
⁸ Chromaleont S.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
⁹ Research Unit of Food Science and Nutrition, Department of Science and Technology for Humans and the Environment, Campus Bio-Medico University of Rome, Rome, Italy.

Abstract

Among the phencyclidine (PCP) and synthetic cathinone analogs present on the street market, 3-methoxyphencyclidine (3-MeO-PCP) is one of the most popular dissociative hallucinogen drugs, while 3-methylmethcathinone (3-MMC) is a commonly encountered psychostimulant. Numerous 3-MeO-PCP- and 3-MMC-related intoxication cases have been reported worldwide. Identification of the positional isomers of MeO-PCP and MMC families are particularly challenging for clinical and forensic laboratories; this is mostly due to their difficult chromatographic separation (particularly when using liquid chromatography-LC) and similar mass spectrometric behaviors. 3-MeO-PCP and 3-MMC were identified in two powders, detained by two subjects and seized by the police, by different analytical techniques, including liquid chromatography-high-resolution accurate-mass Orbitrap mass spectrometry (LC-HRAM-Orbitrap-MS), and solid deposition gas chromatography-Fourier transform infrared spectroscopy (sd-GC-FTIR). LC-HRAM-Orbitrap-MS allowed us to assign the elemental formulae C₁₈H₂₇NO (MeO-PCP) and C₁₁H₁₅NO (MMC) through accurate mass measurement of the two MH⁺ ions, and the comparison of experimental and calculated MH⁺ isotopic patterns. However, MH⁺ collision-induced product ions spectra were not conclusive in discriminating between the positional isomers [(3-MeO-PCP vs. 4-MeO-PCP) and (3-MMC vs. 4-MMC and 2-MMC)]. Likewise, sd-GC-FTIR easily allowed us to differentiate between the MeO-PCP and MMC positional isomers unambiguously, confirming the presence of 3-MeO-PCP and 3-MMC, due to the high-quality match factor of the experimental FTIR spectra against the target FTIR spectra of MeO-PCP and MMC isomers in a dedicated library. 3-MeO-PCP (in contrast to 3-MMC) was also detected in blood and urine samples of both subjects and analyzed in the context of routine forensic casework by LC-HRAM-Orbitrap-MS following a simple deproteinization step. In addition, this untargeted approach allowed us to detect dozens of phase I and phase II 3-MeO-PCP metabolites in all biological specimens. Analysis of the extracted samples by sd-GC-FTIR revealed the presence of 3-MeO-PCP, thus confirming the intake of such specific methoxy-PCP isomer in both cases. These results highlight the effectiveness of LC-HRAM-Orbitrap-MS and sd-GC-FTIR data in attaining full structural characterization of the psychoactive drugs, even in absence of reference standards, in both non-biological and biological specimens.

Keywords: 3-methoxyphencyclidine; 3-methylmethcathinone; forensic toxicology; fourier transform infrared spectroscopy; gas chromatography; liquid chromatography-high-resolution mass spectrometry; non-fatal intoxication; solid deposition GC-FTIR interface.