Fatal case of poisoning with a new cathinone derivative: α-propylaminopentiophenone (N-PP)

Majchrzak, Milena; Skowronek, Rafał; Kowalska, Teresa; Sajewicz, Mieczysław

doi:10.1007/s11419-018-0417-x

Cited by 21 publications

(16 citation statements)

References 16 publications

(18 reference statements)

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“…(perdeuterated on the diethylpropion moiety) in Several structures have been proposed for the loss of H2O from synthetic cathinones; however, the previous studies did not use of isotopic labeling or HRMS [15,17,28,37,77,78]. Our data supports the mechanism proposed in [61].…”

Section: Dart/esi-q-tofsupporting

confidence: 83%

“…5b shows the dominant loss of H2O observed at m/z 149.1160 (C10H9D3N + expected at m/z 149.1154; 4 ppm error) from the [M+H] + protonated precursor at m/z 167.1295 (C10H11D3NO + expected at m/z 167.1260; 21 ppm error). This fragmentation behavior is consistent with previous literature for N-alkylated synthetic cathinones[15, 17,28,36,77]. Note that, unlike the fentanyl analogs, neither methcathinone-d3, nor any of the other synthetic cathinones show sodiated adducts ([M+Na] + ) in the full scan mass spectra.…”

supporting

confidence: 91%

“…Proposed mechanisms for fragmentation pathways of N-alkylated synthetic cathinones. The model compound is pentedrone (aliphatic group=CH3, N-alkyl group=CH3, X=H) with ions specific pentedrone indicated with an asterisk (*); different functional groups, X, will shift the product ion m/z values accordingly.The primary fragmentation pathways for the N-alkylated class of synthetic cathinones are through the loss of H2O (blue pathway), CnH2n+3N (black pathway), and C7H6O (red pathway), which is consistent with previous work by others on this class of compounds[15, 17,28,37,77,78]. The dominant pathway for 2° amines within this class is through the loss of H2O via two hydrogen transfers to the oxygen.…”

supporting

confidence: 87%

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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: Dart/esi-q-tofsupporting

confidence: 83%

supporting

confidence: 91%

supporting

confidence: 87%

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Structural Characterization of Emerging Synthetic Drugs

Davidson¹

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“… 56 More recent in vitro studies in neuronal, skeletal muscle and hepatic cells have demonstrated potentially cytotoxic effects of synthetic stimulant exposure, including mitochondrial dysfunction, glutathione depletion, oxidative stress and apoptosis pathway activation, which are aggravated under hyperthermic conditions; however, the extent to which these mechanisms are relevant to their effects in vivo remains unclear. 56 – 58 …”

Section: Synthetic Stimulantsmentioning

confidence: 99%

“…Case reports have shown synthetic stimulants can induce acute intra-parenchymal and subarachnoid haemorrhages as well as ischemic infarction, 58 and α-PVP has been implicated in ST-elevation myocardial infarction (STEMI) with multiple intra-cardiac thrombi. 59 Intravenous methcathinone (M-CAT) use has been associated with the rare syndrome of manganese-associated Parkinsonism (as the preparation of M-CAT involves use of potassium permanganate) and cognitive impairment, which has been termed ‘ephedrone encephalopathy’.…”

Section: Synthetic Stimulantsmentioning

confidence: 99%

New psychoactive substances: a review and updates

Shafi

Berry

Sumnall

et al. 2020

Therapeutic Advances in Psychopharmacology

175

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New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.

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Comparison of in‐source collision‐induced dissociation and beam‐type collision‐induced dissociation of emerging synthetic drugs using a high‐resolution quadrupole time‐of‐flight mass spectrometer

2021

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In‐source collision‐induced dissociation (CID) is commonly used with single‐stage high‐resolution mass spectrometers to gather both a molecular formula and structural information through the collisional activation of analytes with residual background gas in the source region of the mass spectrometer. However, unlike tandem mass spectrometry, in‐source CID does not involve an isolation step prior to collisional activation leading to a product ion spectrum composed of fragment ions from any analyte present during the activation event. This work provides the first comparison of in‐source CID and beam‐type CID spectra of emerging synthetic drugs on the same instrument to understand the fragmentation differences between the two techniques and to contribute to the scientific foundations of in‐source CID. Electrospray ionization–quadrupole time‐of‐flight (ESI‐Q‐TOF) mass spectrometry was used to generate product ion spectra from in‐source CID and beam‐type CID for a series of well‐characterized fentanyl analogs and synthetic cathinones. A comparison between the fragmentation patterns and relative ion abundances for each technique was performed over a range of fragmentor offset voltages for in‐source CID and a range of collision energies for beam‐type CID. The results indicate that large fragmentor potentials for in‐source CID tend to favor higher energy fragmentation pathways that result in both kinetically favored pathways and consecutive neutral losses, both of which produce more abundant lower mass product ions relative to beam‐type CID. Although conditions can be found in which in‐source CID and beam‐type CID provide similar overall spectra, the in‐source CID spectra tend to contain elevated noise and additional chemical background peaks relative to beam‐type CID.

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Fatal case of poisoning with a new cathinone derivative: α-propylaminopentiophenone (N-PP)

Cited by 21 publications

References 16 publications

Structural Characterization of Emerging Synthetic Drugs

Structural Characterization of Emerging Synthetic Drugs

New psychoactive substances: a review and updates

Comparison of in‐source collision‐induced dissociation and beam‐type collision‐induced dissociation of emerging synthetic drugs using a high‐resolution quadrupole time‐of‐flight mass spectrometer

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