Identification and analytical characterization of nine synthetic cathinone derivatives N‐ethylhexedrone, 4‐Cl‐pentedrone, 4‐Cl‐α‐EAPP, propylone, N‐ethylnorpentylone, 6‐MeO‐bk‐MDMA, α‐PiHP, 4‐Cl‐α‐PHP, and 4‐F‐α‐PHP

Abstract

Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances (NPS) phenomenon. In this study, the analytical characterization of nine synthetic cathinones is described: 2-(ethylamino)-1-phenylhexan-1-one (N-ethylhexedrone 1), 1-(4-chlorophenyl)-2-(methylamino)pentan-1-one (4-Cl-pentedrone 2), 1-(4-chlorophenyl)-2-(ethylamino)pentan-1-one (4-Cl-α-EAPP 3), 1-(3,4-methylenedioxyphenyl)-2-propylaminopropan-1-one (propylone 4), 1-(3,4-methylenedioxyphenyl)-2-ethylaminopentan-1-one (N-ethylnorpentylone 5), 1-(6-methoxy-3,4-methylenedioxyphenyl)-2-methylaminopropan-1-one (6-MeO-bk-MDMA 6), 4-methyl-1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PiHP 7), 1-(4-chlorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-Cl-α-PHP 8), and 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexan-1-one (4-F-α-PHP 9). The identification was based on ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. The mass-spectral fragmentations of these compounds following collision-induced dissociation (CID) and electron ionization (EI) were studied to assist forensic laboratories in identifying these compounds or other substances with similar structure in their case work. To our knowledge, no analytical data about the compounds 1-4, 7, and 8 have appeared until now, making this the first report on these compounds. The GC-MS data of 5, 6 and 9 has been reported, but this study added the LC-MS, Fourier Transform Infrared (FTIR) and NMR data for additional characterization. Copyright © 2016 John Wiley & Sons, Ltd.

The mechanism of water loss from protonated cathinones

“…For example, the fragmentation of the [M + H− H 2 O] + ion of buphedrone involves the loss of an ethyl radical (formation of the product ion at m/z 131, Figure ). This is in good agreement with the fragmentation of [M + H − H 2 O] + ions of cathinones reported by Liu et al A careful examination of the fragmentation of other nitrogen three‐membered‐ring‐containing ions leads to the conclusion that the violation of the even‐electron rule is a feature of such ions . This confirms that [M + H − H 2 O] + ions contain an azirine ring (scheme ).…”

“…As clearly seen from Figures and S1–S7, the eliminated H 2 O molecules do not contain hydrogen atoms attached to the chiral carbon atom (a loss of mass 20 from [M(D) + D] + ions occurs!). This is strong evidence that the mechanism shown in scheme is not valid and the hydrogen atom attached to the chiral carbon atom is not involved in the process of H 2 O loss from [M + H] + ions as proposed elsewhere . The only question is whether the fragment ion at m/z 161 in the product ion spectrum of [M(D) + D] + is the [M( 13 C)(D) + D‐D 2 O] + ion or the [M(D) + D − HDO] + ion.…”

“…The electron ionization (EI) mass spectra of these compounds show no molecular ions; thus, high‐performance liquid electrospray/electrospray ionization mass spectrometry (HPLC/ESI‐MS) seems to be a much better technique than gas chromatography/EI‐MS for their identification . Well documented in the literature, the fragmentation pathways of [M + H] + ions (generated by ESI‐MS) of synthetic cathinones may be useful for their identification …”

“…[6][7][8][9][10] Well documented in the literature, the fragmentation pathways of [M + H] + ions (generated by ESI-MS) of synthetic cathinones may be useful for their identification. [11][12][13][14][15][16][17][18][19][20][21] The only fragmentation pathway that, in our opinion, has not been properly described is the mechanism of the loss of a water molecule from [M + H] + ions. In our opinion, the loss of H 2 O occurs only for those cathinones that contain the -NH-R moiety (secondary amines), as can be deduced from the published ESI mass spectra.…”

Spectroscopic characterization and crystal structures of four hydrochloride cathinones: N-ethyl-2-amino-1-phenylhexan-1-one (hexen, NEH), N-methyl-2-amino-1-(4-methylphenyl)-3-methoxypropan-1-one (mexedrone), N-ethyl-2-amino-1-(3,4-methylenedioxyphenyl)pentan-1-one (ephylone) and N-butyl-2-amino-1-(4-chlorophenyl)propan-1-one (4-chlorobutylcathinone)

“…Analyzed substances were seized by police; they were presented as unlabeled white powder samples. Three of them had been characterized chromatographically (compounds 1 [8], 2 [9], and 3 [10]). Compound 4 has not been characterized yet (chromatographically or spectroscopically).…”