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.
Highlights
The new psychoactive substances (NPS) phenomenon, characterized by peculiar features as opposed to the traditional drug phenomena (Peacock et al, 2019; Zamengo et al, 2019), has emerged as a global threat that challenges public health and institutions (UNODC, 2020)
We attained the full identification of the two NPS under study, in both non-biological (3-MMC and 3-MeO-PCP) and biological (3-MeO-PCP) specimens, through a combination of gas chromatography (GC)-EI mass spectrometry (MS), liquid chromatography (LC)-HRAM-Orbitrap-MS, and sd-GC-Fourier Transform Infrared Spectroscopy (FTIR), without resorting to specific reference standards
The results described in this paper highlight the effectiveness of LCHRAM-Orbitrap-MS and sd-GC-FTIR in attaining the full structural characterization of 3-MMC and 3-MeO-PCP in seized products, the identification of 3-MeO-PCP and numerous phase I and phase II metabolites in blood, plasma, and urine samples of both cases, and the discrimination between the MMC and MeO-PCP positional isomers [(3-MMC vs. 4-MMC and 2-MMC) and (3-MeO-PCP vs. 4MeO-PCP)] in both non-biological and biological specimens
Summary
The new psychoactive substances (NPS) phenomenon, characterized by peculiar features as opposed to the traditional drug phenomena (Peacock et al, 2019; Zamengo et al, 2019), has emerged as a global threat that challenges public health and institutions (UNODC, 2020). Individual products may contain multiple psychoactive ingredients, adulterants, or byproducts in extremely variable concentrations, exposing consumers to unpredictable doses of multiple NPS with serious health-related consequences, especially in young people (Zamengo et al, 2014; Orsolini et al, 2019; Larabi et al, 2020). According to their effects, dissociatives, sedatives/hypnotics, synthetic opioids, hallucinogens, synthetic cannabinoid receptor agonists, and psychostimulants are the NPS that most frequently appear on the recreational drug market (UNODC, 2020). Several 3MMC-related non-fatal and fatal intoxication cases have been described (Bäckberg et al, 2015b; Jamey et al, 2016; Ameline et al, 2019a; Margasinska-Olejak et al, 2019)
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