Identification of novel fragmentation pathways and fragment ion structures in the tandem mass spectra of protonated synthetic cathinones

Structural Characterization of Emerging Synthetic Drugs

“…(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]. Similar to the α-pyrrolidinophenones studied previously [75], which have a facile leaving group in the form of pyrrolidine, fragmentation via the loss of a neutral 3° amines was the dominant fragmentation pathway for the 3° amines analyzed here.…”

“…These spectra demonstrate that both ion sources produce similar mass spectra with the base peak observed at m/z 105.0727 (expected at m/z 105.0704 for C8H9 + ; 22 ppm error) for the ESI-generated mass spectrum. The formation of this ion is unexpected in that the isotopically labeled carbonyl adjacent to the aromatic ring moiety must be lost prior to ring expansion, which has been previously demonstrated as a possible fragmentation mechanism of α-pyrrolidinophenone synthetic cathinones[61].z 204.1355 (expected at m/z 204.1338 for C12 13 CH17ON +˙; 8 ppm error), m/z 190.1315 (expected at m/z 190.1307 for C12 13 CH17O + ; 4 ppm error), and m/z 140.14535 (expected at m/z 140.1439 for C9H18N + ; 10 ppm error) for the ESI-generated mass spectrum originate through the loss of a butyl radical (˙C4H9), loss of the pyrrolidine molecule, and the generation of the 1pentylidenepyrrolidin-1-ium ion, respectively. The tertiary product ions at m/z 134.0725 (expected at m/z 134.0681 for C8 13 CH9O + ; 33 ppm error) and m/z 120.0540 (expected at m/z 120.0524 for C713 CH7O + ; 13 ppm error) for the ESI -generated mass spectrum form through the loss of butylene and stepwise loss of C5H10 from the primary product ion at m/z 190.1315 (C12 13 CH17O + ).…”

“…For example, when valid mechanisms have been proposed, the lack of isotopic labeling and lack of multi-stage mass spectrometry (MS n ) limit the certainty associated with the proposed mechanisms [30]. Recently, we demonstrated the first use of isotopic labeling, multi-stage mass spectrometry (MS n ), accurate mass measurements with high-resolution mass spectrometry (HRMS) and ion spectroscopy to explain the formation of the tropylium ion (m/z 91) and its substituted derivatives for α-pyrrolidinophenone synthetic cathinones analyzed with ESI-MS/MS [61]. Here, we extend the study to a wider variety of α-pyrrolidinophenone synthetic cathinone structures and include fragmentation pathways accessed through radical and even-electron pathways.…”

“…Our previous work with α-pyrrolidinophenone synthetic cathinones involved the identification that the tropylium ion (m/z 91) or substituted derivative ions form through different oxygencontaining intermediates that exclusively retain the α-carbon with the corresponding loss of the carbonyl carbon as neutral CO [61]. Through this project we also discovered several fragmentation behaviors of the α-pyrrolidinophenone class of synthetic cathinones.…”

“…The comparison of the fragmentation mechanisms of odd-electron ions (EI) and even-electron ions (ESI) provides a more comprehensive understanding of the differences in fragmentation behavior.The fragmentation behavior of N-alkylated synthetic cathinones has been reported throughout literature; however, the underlying fragmentation mechanisms that lead to the observed fragment ions are rarely discussed or understood[13,32,37,71]. Examples of the confusion about the formation of the tropylium ion from protonated synthetic cathinones have been highlighted previously by our group[61]. Even when mechanisms have been proposed, the lack of isotopic labeling and multi-stage mass spectrometry limits the certainty associated the proposed mechanisms[28].…”