Fragmentation pathways of odd- and even-electron N-alkylated synthetic cathinones

Davidson, J. Tyler; Sasiene, Zachary J.; Jackson, Glen P.

doi:10.1016/j.ijms.2020.116354

Cited by 23 publications

(39 citation statements)

References 27 publications

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“…The beam-type CID spectra in from the N-alkyl chain, respectively. The presence of even-electron intermediates fragmenting into odd-electron product ions has been reported before for N-alkylated synthetic cathinones [36,37,152].…”

Section: Discussion Of Fentanyl Analogssupporting

confidence: 62%

“…The goal of this study is to qualitatively analyze the product ion spectra generated with insource CID and beam-type CID for a series of fentanyl analogs and synthetic cathinones that have been previously well characterized [106,152]. The Q-TOF mass spectrometer allows simultaneous collection of full scan (containing in-source CID product ions) and beam-type CID product ion spectra, thereby allowing the comparison of mass spectra generated under conditions as similar as possible [138].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work with N-alkylated synthetic cathinones demonstrated that, whereas 2° amines favor the loss of water, 3° amines favor the formation of alkylphenones and a corresponding iminium counter ion [152]. The common phenylethyl ion at m/z 105.0713 and phenylium ion at m/z 77.0397 were also identified [34].…”

Section: Discussion Of Fentanyl Analogsmentioning

confidence: 99%

“…Through the analysis of a series of N-alkylated synthetic cathinones, we have identified the general consistency between product ion spectra of in-source CID and beam-type CID on the same instrument with the same ion source. The compounds analyzed had a range of molecular weights and various degrees of substitution, including the presence of 2° and 3° amines, which are known to favor different pathways during tandem mass spectrometry [152]. Whereas in-source CID and beam-type CID spectra are generally similar in the distribution and types of product ions formed, the spectra can be distinguished based on subtle differences in relative ion abundances and by the fact that the in-source CID spectra typically provide increased noise and additional adducts relative to beam-type CID spectra.…”

Section: Discussion Of Synthetic Cathinonesmentioning

confidence: 99%

“…The analysis of a series of previously characterized fentanyl analogs [106] and synthetic cathinones [152] with a Q-TOF mass spectrometer allowed for a qualitative assessment of the similarities and differences in the product ion spectra generated with in-source CID and beam-type CID conditions. In this study, we demonstrate that, under certain conditions, it is possible to generate visually similar product ion spectra between in-source CID and beam-type CID of the same substance.…”

Section: Discussionmentioning

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: Discussion Of Fentanyl Analogssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussion Of Fentanyl Analogsmentioning

confidence: 99%

Section: Discussion Of Synthetic Cathinonesmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Structural Characterization of Emerging Synthetic Drugs

Davidson¹

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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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Detection, discrimination and quantification of amphetamine, cathinone and nor‐ephedrine regioisomers using benchtop ¹H and ¹⁹F nuclear magnetic resonance spectroscopy

Hulme

Hayatbakhsh

Brignall

et al. 2021

Magnetic Reson in Chemistry

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Fragmentation pathways of odd- and even-electron N-alkylated synthetic cathinones

Cited by 23 publications

References 27 publications

Structural Characterization of Emerging Synthetic Drugs

Structural Characterization of Emerging Synthetic Drugs

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

Detection, discrimination and quantification of amphetamine, cathinone and nor‐ephedrine regioisomers using benchtop ¹H and ¹⁹F nuclear magnetic resonance spectroscopy

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Fragmentation pathways of odd- and even-electron N-alkylated synthetic cathinones

Cited by 23 publications

References 27 publications

Structural Characterization of Emerging Synthetic Drugs

Structural Characterization of Emerging Synthetic Drugs

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

Detection, discrimination and quantification of amphetamine, cathinone and nor‐ephedrine regioisomers using benchtop 1H and 19F nuclear magnetic resonance spectroscopy

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Detection, discrimination and quantification of amphetamine, cathinone and nor‐ephedrine regioisomers using benchtop ¹H and ¹⁹F nuclear magnetic resonance spectroscopy