Reporting the novel synthetic cathinone 5-PPDI through its analytical characterization by mass spectrometry and nuclear magnetic resonance

Fabregat‐Safont, David; Carbón, Xoán; Gil, Cristina; Ventura, Montserrat Carbonell; Sancho, Juan V.; Hernández, Félix

doi:10.1007/s11419-018-0422-0

Cited by 17 publications

(20 citation statements)

References 22 publications

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“…propose an unsupported 'shift' of the carbonyl group to explain the equivalent ion at m/z 135 for 3,4-MDPV [27]. Similarly, Pozo et al, Fabregat-Safont et al, and Qian et al propose mechanisms that involve the loss of CO directly from the aliphatic chain during the fragmentation of synthetic cathinones without the use of isotopic labeling to support these conclusions [28][29][30]. Our work now supports these proposed losses of CO.…”

Section: Introductionsupporting

confidence: 77%

“…The fragmentation behavior of α-pyrrolidinophenone synthetic cathinones has been reported throughout literature; however, rarely are the underlying fragmentation mechanisms that lead to the observed fragment ions discussed or understood [14,16,20,[26][27][28][29]. Instead, the mechanism(s) are either absent, vague, or improbable.…”

Section: B) A)mentioning

confidence: 99%

“…4b, respectively, is particularly interesting. Although the loss of CO directly from the alkyl chain had been proposed by Pozo et al[28], Fabregat-Safont et al[29] and Qian et al[30], this pathway had not been verified until the current use of isotopic labeling.The MS n fragmentation of the precursor ion [M+H] + at m/z 234 for18 O-α-PVP results in the formation of primary product ions at m/z 214, 191, 163, and 156(Figure 1.5a). The primary product ions, except for m/z 214, are all shifted by two Daltons (Da) relative to the same product…”

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confidence: 99%

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Structural Characterization of Emerging Synthetic Drugs

Davidson¹

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Structural Characterization of Emerging Synthetic Drugs J. Tyler Davidson The identification of well-characterized seized drugs is performed thousands of times a day in the United States; however, the expanding use of emerging synthetic drugs is creating a growing problem for both toxicological and seized drug analyses. Two of the most rapidly growing areas of emerging synthetic drugs are synthetic cathinones and fentanyl-related compounds (FRCs). In this work we demonstrate the combination of multi-stage mass spectrometry (MS n), accurate mass measurements with high-resolution mass spectrometry (HRMS), and isotopic labeling for the structural characterization of synthetic cathinones and fentanyl analogs. The deliverables of this research include the identification of conserved fragmentation pathways for synthetic cathinones and fentanyl analogs, proposed mechanisms for the formation of characteristic ions through both protonated tandem mass spectrometry (MS/MS) and electron ionization mass spectrometry (EI-MS), and a discussion about how to apply the broadened understanding of the fragmentation behavior to the identification of novel synthetic cathinones and fentanyl analogs. The first major finding about the fragmentation behavior of synthetic cathinones is that the tropylium ion (m/z 91), or substituted derivative thereof, forms through different oxygencontaining intermediates that do not contain a formal C=O bond but instead contain a phthalanelike core structure. The phthalane-like intermediates were elucidated through gas-phase ion spectroscopy measurements and density functional theory (DFT) calculations. Likewise, the use of stable isotope labeling revealed the unprecedented finding that, during collision-induced dissociation (CID) of α-pyrrolidinophenone synthetic cathinones, the α-carbon is retained almost exclusively in the tropylium ion and the carbonyl carbon is not retained in the tropylium ion. Isotope labeling also identified competitive pathways for the loss of CO and ethylene (C2H4) from a primary intermediate ion, which provides support for the direct loss of CO from the alkyl side chain. A second major finding was the identification of characteristic protonated MS/MS fragmentation pathways and proposed mechanistic origins for both protonated MS/MS and EI-MS fragmentation for α-pyrrolidinophenone and N-alkylated synthetic cathinones. For MS/MS spectra of protonated α-pyrrolidinophenone synthetic cathinones the dominant fragmentation pathways are through 4-center hydrogen rearrangements to produce pyrrolidine ring cleavage, characteristic iminium ions and diagnostic ions at m/z 91 and m/z 105. For EI mass spectra, radical-directed αcleavages result in dominant iminium ions. In contrast to α-pyrrolidinophenone synthetic cathinones, MS/MS of protonated N-alkylated synthetic cathinones provided abundant radical losses from both the N-alkylated and aliphatic side chains, a dominant loss of H2O for 2° amines and the formation of abundant alkylphenones for 3° amines. These findings help advance our cu...

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Section: Introductionsupporting

confidence: 77%

Section: B) A)mentioning

confidence: 99%

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confidence: 99%

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Structural Characterization of Emerging Synthetic Drugs

Davidson¹

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“…UHPLC coupled to mass spectrometry (MS) plays an essential role in cathinone analysis, using both high-resolution MS (HRMS) and low-resolution MS/MS. Thus, most studies about the identification of novel cathinones [31][32][33] and the elucidation of their metabolites [34][35][36] have utilized UHPLC-HRMS, taking profit of the full-spectrum acquisition and high mass accuracy provided by this technique. UHPLC-MS/MS is the preferred technique for the accurate and sensitive determination of a predetermined list of compounds, and has often been used for studying the pharmacokinetics and pharmacodynamics of cathinones 20,[37][38][39][40] .…”

Section: Introductionmentioning

confidence: 99%

Understanding the pharmacokinetics of synthetic cathinones: Evaluation of the blood–brain barrier permeability of 13 related compounds in rats

et al. 2020

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Synthetic cathinones are the second most commonly seized new psychoactive substance family in Europe. These compounds have been related to several intoxication cases, including fatalities. Although the pharmacological effects, metabolism, and pharmacokinetics of cathinones have been studied, there is little information about the permeability of these compounds through the blood–brain barrier (BBB). This is an important parameter to understand the behavior and potency of cathinones. In this work, 13 selected cathinones have been analyzed in telencephalon tissue from Sprague–Dawley rats intraperitoneally dosed at 3 mg/kg. Our results revealed a direct relationship between compound polarity and BBB permeability, with higher permeability for the more polar cathinones. The chemical moieties present in the cathinone had an important impact on the BBB permeability, with lengthening of the α‐alkyl chain or functionalization of the aromatic ring with alkyl moieties resulting in lower concentration in telencephalon tissue. Our data suggest that transport of cathinones is a carrier‐mediated process, similar to cocaine transport across the BBB.

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“…Synthetic cathinones are, nowadays, the second largest group of new psychoactive substances (NPS) monitored by the EMCDDA, and the most frequently seized NPS in 2015 1 . In the last years, the characterization of novel synthetic cathinones has been an on-going topic for forensic laboratories, showing that modifications of the cathinone moieties are the most frequent option for the production of novel stimulants 2–9 . Nonetheless, the number of new synthetic cathinones reported every year is decreasing 1 , and the effects profile of the newest cathinone derivatives as reported by users have been unfavourable (especially when compared to older cathinone analogues) 10 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of a recently detected halogenated aminorex derivative: para-fluoro-4-methylaminorex (4′F-4-MAR)

Fabregat‐Safont

Carbón

Ventura

et al. 2019

Sci Rep

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Despite the fact that 33% of the new psychoactive substances seized in 2015 were synthetic cathinones, the number of these derivatives has been decreasing in the last years, probably as a consequence of the unfavourable effects reported by users. Thus, the list of possible cathinone analogues is expected to get shorter, and it is likely that the same moiety changes applied for the preparation of synthetic cathinones will be applied in the near future to other stimulants in the search for favourable alternatives to controlled substances. This is evidenced by the increase in newly reported substances belonging to stimulant classes other than cathinones. One of the possible candidates for a new backbone from which to base new stimulants is aminorex, which is classified as a Schedule I substance by the Drug Enforcement Administration. Three derivatives have been reported until now: 4-methylaminorex or 4-MAR (also categorized as a Schedule I substance), para-methyl-4-methylaminorex (4,4′-DMAR) and 3′,4′-methylenedioxy-4-methylaminorex (MDMAR). Recently, the new halogenated 4-MAR derivative, para-fluoro-4-methylaminorex, characterised in this work (and abbreviated as pF-4-methylaminorex or 4′F-4-MAR) was detected by the Slovenian police. In the present work, 4′F-4-MAR has been characterized by high resolution mass spectrometry and nuclear magnetic resonance in a sample obtained from an anonymous consumer. This research shows that the same modifications applied for the preparation of synthetic cathinones are being used to prepare new stimulants based on the aminorex backbone.

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Reporting the novel synthetic cathinone 5-PPDI through its analytical characterization by mass spectrometry and nuclear magnetic resonance

Cited by 17 publications

References 22 publications

Structural Characterization of Emerging Synthetic Drugs

Structural Characterization of Emerging Synthetic Drugs

Understanding the pharmacokinetics of synthetic cathinones: Evaluation of the blood–brain barrier permeability of 13 related compounds in rats

Characterization of a recently detected halogenated aminorex derivative: para-fluoro-4-methylaminorex (4′F-4-MAR)

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