J. D. Power et al.
[M + H]+ ion, as previously reported, was observed.[6] The
base peak, m/z 131 (ion H), in the three compounds arises
from subsequent loss of the a alkyl chain (Fig. 5 and Table 1).
The m/z 130 ion (ion B, Fig. 5), prominent in the spectra of
cathinone derivatives 1–3, had the formula C9H8N, and is
formed by the loss of methane from the [M + H – H2O]+ ion
in 1 whereas in compounds 2 and 3 it arises from initial loss
of a methyl radical, followed by loss of a further methyl or
ethyl radical, respectively. The precursor ions were identified
as m/z 146 (1), 145 (2) and 159 (3). The m/z 144 ion (ion G,
C10H10N) in the mass spectra of 2 and 3 was found to arise
from the [M + H – H2O]+ ion by loss of methane and ethane,
respectively. Interestingly, the m/z 105 ion is predominately
C8H9 (ion E, Fig. 5, precursor ion m/z 133) in 1 and C7H5O
([PhCO]+, ion D, precursor ions m/z 147 and 161, respectively)
in compounds 2 and 3 (Fig. 6). The [M + H – 33]+ ion (m/z 131,
145 and 159, respectively) in the three compounds was not
due to the loss of CH5N (methylamine and hydrogen) from
the [M + H]+ ion, as had been previously reported, but
resulted from the loss of water and a methyl radical.[5] For
the three N-ethyl derivatives (compounds 4–6), loss of ethene
from the [M + H – H2O]+ ion produces m/z 132, 146 and 160,
respectively, while the m/z 131, 145 or 159 ions were formed
by loss of an ethyl radical (Fig. 5 and Table 2). The C9H8N
ion (m/z 130) was again observed in the three spectra with
the precursor ions being identified as m/z 131 and 145 (4),
m/z 145 (5), and m/z 159 (6).
compounds were readily resolved by LC (Fig. 3). Their in-
source product ion mass spectra were found to be quite differ-
ent and, overall, LC/MS was found to be superior to GC/MS
in distinguishing the two compounds. Significant differences
in the mass spectra included (i) a more dominant m/z 91 ion
in buphedrone (2), (ii) relatively more intense m/z 105
and 117 ions in ethcathinone (4), (iii) the relative intensi-
ties of the m/z 130/131/132 cluster, and (iv) the ratio of
the [M + H]+/([M + H – H2O]+) ions. The relatively higher
intensity of the m/z 105 ion in ethcathinone (4) may be
explained by the fact that it is comprised of both [C6H5O]+
and [C9H8]+ ions. A library of 22 cathinone derivatives
commonly encountered during the course of our forensic
investigations was constructed and, apart from 3- and
4-flephedrone, excellent discrimination is observed with a
range of derivatives including ring-substituted compounds
(Table 5).
Overall, it was found that product ion mass spectra
produced by in-source CID following ESI have potential for
use in the routine forensic analysis of cathinone derivatives
but one challenge to be overcome is to change the analysts’
’mind-set’ away from the traditional use of the widely used
and accepted electron ionization that normally accompanies
GC. The reproducibility of in-source CID across instruments
may be a limiting factor and some optimization will be
needed for different instruments. However, in the context of
its use in accredited forensic laboratories, such optimization
would be a normal practice, as all new methods have to be
fully validated before use. It has been also suggested that
the reproducibility problem may be overcome by the use of
library search algorithms that are weighted to the m/z values
of the ions and not to absolute abundances.[7,17]
Having established that product ion mass spectra offer
useful structural information and are readily interpreted, a
simpler single quadrupole electrospray mass spectrometer
(Agilent 1100 MSD) with in-source CID was then evaluated.
A fragmentor voltage of 120 V was found to produce mass
spectra similar to those obtained with a 45% NCE on the
™
LTQ/Orbitrap . The recommended working range for the
fragmentor voltage is between 30 and 150 V and it was
found that working above 120 V could result in complete loss
of the [M + H]+ ion with N-methyl-a-methyl cathinone
derivatives such as methcathinone. A library containing
the in-source product ion mass spectra of compounds 1–6
CONCLUSIONS
It has been shown that the in-source product ion mass spectra of
cathinone derivatives are readily interpretable and useful for
the identification of this type of drug. Electrospray ionization
mass spectrometry is widely used for molecular weight deter-
mination in the course of forensic drug analysis but it has been
demonstrated here that, with suitable dissociation conditions,
its usefulness may be extended to produce more informative
mass spectra facilitating the discrimination of closely related
cathinone derivatives. Although the technique may require some
adaptation for different instrument platforms, this drawback is
outweighed by the fact that it provides both molecular weight
and structural information not obtainable when cathinone
derivatives are analyzed by the more conventional GC/EIMS
methodology. A generalized product ion formation scheme
for the cathinone derivatives has been also formulated.
™
was created using Chemstation software (version G1701D,
Agilent Technologies) and, from comparison of the library
matches using the software’s probability-based match (PBM)
algorithm, excellent discrimination of the compounds was
observed (Table 3).[14,15] To further investigate the feasibility
of utilizing in-source product ion mass spectra to identify
™
cathinone derivatives, an Agilent Chemstation library of five
isobaric compounds (C12H17NO, M = 191, Table 4), was created.
All these compounds produced an [M + H]+ ion and an
[M + H – H2O]+ ion (10–20% abundance) when the fragmentor
voltage was set at 70 V on the Agilent 1100 MSD. Increasing
the in-source fragmentation voltage to 120 V resulted in
significant and reproducible product ion formation, and
much improved discrimination, greatly facilitating the iden-
tification of 4-methylethcathinone (4-MEC) in a ’bath salts’
product encountered during routine forensic analysis (Table 4).
In another instance, the use of in-source product ion mass
spectra facilitated the identification of a change of the active
ingredient from ethcathinone (compound 4) to buphedrone
(compound 2) in a ’bath salts’ product. The compounds were
difficult to separate by GC and their EI mass spectra were
found to be very similar with a low mass m/z 44 ion
being the major distinguishing factor.[16] However, the two
REFERENCES
[1] J. P. Kelly. Cathinone derivatives: A review of their chemistry,
pharmacology and toxicology. Drug Test. Anal. 2011, 3, 439.
[2] European Monitoring Centre for Drugs and Drug Addic-
tion (EMCDDA). Synthetic cathinones. Available: http://
wileyonlinelibrary.com/journal/rcm
Copyright © 2012 John Wiley & Sons, Ltd.
Rapid Commun. Mass Spectrom. 2012, 26, 2601–2611
Power, John D.
