See

discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/264709058

Erratum to Acute combined poisoning with

the new designer drug 4-methyl-N-ethylcathinone (4-MEC) and gammabutyrolactone
(GBL): A case report with different analytical
approaches...
Article September 2014
DOI: 10.1016/j.toxac.2014.07.001

READS

119

8 authors, including:
David Boels

Andreas G Helfer

Centre Hospitalier Universitaire d'Angers

Universitt des Saarlandes

40 PUBLICATIONS 71 CITATIONS

14 PUBLICATIONS 43 CITATIONS

SEE PROFILE

SEE PROFILE

Benedicte Lelievre

Markus Meyer

University of Angers

Universitt Heidelberg

39 PUBLICATIONS 105 CITATIONS

125 PUBLICATIONS 1,733 CITATIONS

SEE PROFILE

All in-text references underlined in blue are linked to publications on ResearchGate,

letting you access and read them immediately.

SEE PROFILE

Available from: David Boels

Retrieved on: 19 April 2016

This article appeared in a journal published by Elsevier. The attached

copy is furnished to the author for internal non-commercial research
and education use, including for instruction at the authors institution
and sharing with colleagues.
Other uses, including reproduction and distribution, or selling or
licensing copies, or posting to personal, institutional or third party
websites are prohibited.
In most cases authors are permitted to post their version of the
article (e.g. in Word or Tex form) to their personal website or
institutional repository. Authors requiring further information
regarding Elseviers archiving and manuscript policies are
encouraged to visit:
http://www.elsevier.com/authorsrights

Author's personal copy

Toxicologie Analytique & Clinique (2014) 26, 119127

Disponible en ligne sur

ScienceDirect
www.sciencedirect.com

ORIGINAL ARTICLE

Acute combined poisoning with the new designer

drug 4-methyl-N-ethyl-cathinone (4-MEC) and
gammabutyrolactone (GBL): A case report with
different analytical approaches for identication of
some metabolites
Alain Turcant a,, David Boels b, Andreas G. Helfer c,
Sverine Ferec a, Marie Bretaudeau-Deguigne b,
Bndicte Lelivre a, Markus R. Meyer c,
Hans H. Maurer c
a

Laboratoire de pharmacologie-toxicologie, institut de biologie en sant, centre hospitalier

universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
b
Centre anti-poison, centre hospitalier universitaire, Angers, France
c
Department of experimental and clinical toxicology, Saarland university, Homburg/Saar,
Germany
Received 5 May 2014; received in revised form 1st July 2014; accepted 1st July 2014
Available online 12 August 2014

KEYWORDS
4-MEC;
Metabolites;
HPLC-DAD;
GC-MS;
UPLC-MS/MS;
LC-HR-MS/MS

Summary
Objective. 4-Methyl-N-ethylcathinone (4-MEC) is a novel designer drug of the -keto
amphetamine family. A case of a mixed poisoning by 4-MEC and gamma-butyrolactone (GBL)
is described. Two and half hours after an injected 0.250.5 g 4-MEC dose and thirty minutes
after GBL ingestion, a 39-year-old man became unconscious and presented after admission
to the hospital, transient apnea needing oxygenation and stimulation. After 30 min, he woke
up, but remained confused for 4 hours. He was discharged 13 hours later without particular
symptoms. For conrmation of the poisoning, different analytical procedures such as HPLCUV/DAD, GC-MS, UPLC-MS/MS, and LC-HR-MS/MS were applied. Blood and urine levels (8 h after
injection) were respectively 353 g/L and 100 mg/L for 4-MEC and 300 mg/L and 1000 mg/L for

Corresponding author.
E-mail address: alturcant@chu-angers.fr (A. Turcant).

http://dx.doi.org/10.1016/j.toxac.2014.07.001
2352-0078/ 2014 Socit Franc
aise de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.

Author's personal copy

120

A. Turcant et al.
gamma-hydroxybutyric acid. In urine, three metabolites (dihydro-, nor-, and nor-dihydro-4MEC) could be identied for the rst time and were similar to those described for other
molecules of this class.
aise de Toxicologie Analytique. Published by Elsevier Masson SAS. All
2014 Socit Franc
rights reserved.

Introduction

Experimental

Since several years, the use of recreational drugs, also

called legal highs or designer drugs, is increasing particularly due to the easy access via the web market. These
new synthetic drugs are often phenethylamine-derived substances. Besides the well-known ecstasy compounds, the
-keto amphetamines are more and more consumed [1].
Cathinone, a natural product from Khat (Catha edulis), is the
chemical lead and mephedrone (4-methyl-methcathinone)
was one of the rst derivative (Fig. 1). Overdose of such
psychostimulant cathinones lead to elevated body temperature, sweating, convulsions, but also hallucinations and
paranoia [2]. In July 2012, the entire cathinone group was
scheduled in France. Different analytical approaches for
biological samples and clinical data from exposure were
reported either for mephedrone or other derivatives such
as methylone, butylone, ephedrone, pentedrone [1,38].
Only one case with three patients exposed to 4-methylethcathinone (4-MEC) was reported so far [9] (Fig. 1).
Gamma-butyrolactone (GBL) is an analogue and precursor of gamma-aminobutyric acid (GHB) usually sold as liquid
preparation for recreational use but also use as wheelcleaner. It is rapidly and extensively metabolized in GHB
by the body, and, so, its clinical effects are similar to GHB
effects [10]. Analytical detection of GHB is generally performed by GC/MS after derivatization using trimethylsilyl
(TMS) reagents.
A case of mixed poisoning of 4-MEC and GBL will be
reported here including the analytical strategy and the identication of some MEC metabolites.

Chemicals and reagents

4-MEC, Na-GHB, d6-Na-GHB (1 mg/mL methanolic solution) and the 6 deuterated analogues of amphetamine
(d5-AM), metamphetamine (d5-MA), methylenedioxyamphetamine (d5-MDA), methylenedioxymetamphetamine
(d5-MDMA), methylenedioxyethylamphetamine (d5-MDEA),
methylenedioxybutanamine (d5-MBDB), all in 0.1 mg/mL
methanolic solution, were obtained from LGC Standards
(Molsheim, France), 4-methylephedrine and 4-methylN-ethyl-norephedrine from Euromedex (Strasbourg,
France), methyl-milnacipran from Pierre Fabre laboratories (Castres, France), heptauorobutyric anhydride
(HFBA)
and
N,O-bis-trimethylsilyl-triuoroacetamide
(BSTFA) trimethylchlorosilane (TMCS) from Sigma-Aldrich
(Lyon, France). Methanol and acetonitrile were HPLC grade
and all other reagents were analytical grade. Blank plasma
samples were obtained at a French blood bank (EFS Nantes,
France).

Immunoanalysis
Urine sample was tested with 3 different systems: immunoenzymatic (IE) reagents (Multigent Amphetamine and
Ecstasy) on ARCHITECT C16000 automate (Abbott, Rungis,
France), uorescence polarization immunoassay (FPIA ) on
AXSym system (Abbott, Rungis, France) and Multiline-5
immuno-chromatographic (IC) tests (BMD-Theradiag, Marne
la Valle, France).

Samples preparation procedure

Case report
A 39-year old man, known as poly-drug user, injected a supposed 0.250.50 g dose of 4-MEC. Two and half hours later,
he continued his trip with insufation of a cold spray containing 2-chloroethane, and a short time later, he ingested
gamma-butyrolactone (GBL) as a wheel-cleaner product
given by a friend. Thirty minutes later, he was found unconscious by his friend who called the emergency unit. In the
hospital, about 5 hours after 4-MEC injection, the patient
showed transient apnea needing stimulation and oxygenation. He woke up 30 min later but remained confused for
4 hours. Both blood and urine samples were taken 8 hours
after 4-MEC injection for further toxicological analyses.
Blood and urine alcohol were negative. The patient was
discharged 13 hours after admission and no sequelae were
noted at the three-month survey. The powder bought from
a Dutch website was also submitted for analysis.

General unknown screening with HPLC-UV/DAD was performed on 500 L of plasma or urine using two different
liquid-liquid extraction processes either using simple alkaline conditions for the rst one and alkaline conditions
followed by back-acidic extraction with 0.02 M hydrochloric
acid for the second one as described previously [11].
GC-MS was performed to look for amphetamine derivatives. Plasma or urine (500 L) was extracted under alkaline
conditions by diethyl ether (5 mL) after adding 20 L of the 6
deuterated analogues (5 mg/L). The organic layer was then
evaporated after adding 50 L of a methanol/30% hydrochloric acid mixture (97.5/2.5) and the residue was derivatized
by HFBA (50 L) in an equal volume of ethyl acetate for
20 min at 70 C. After nal evaporation of the reagent, the
residue was dissolved with 100 L ethyl acetate. Injection
volume was 1 L.
The quantitative analysis was performed by UPLC-MS/MS
after a simple protein precipitation of 100 L of plasma or

Author's personal copy

Acute combined poisoning with the new designer drug 4-MEC and GBL: A case report

(b)

DAD1 A, Sig=230,4 Ref=550,100 (MAI2013\0524-015.D)

mAU
160

NH2

7.557

4.838

(a)

121

140

EI
120

100

40

Figure 1. Chemical structures of cathinone (a), mephedrone (b)

and 4-methyl-N-ethcathinone (4-MEC) (c).

Apparatus and analytical conditions

HPLC-UV/DAD (HP1100 or 1200 systems, Agilent, Les Ulis,
France) was performed on a Uptisphere ODB 5 m column
(100 2.1 mm I.D., Interchim, Montluc
on, France) and with
chromatographic conditions already described [11]. GC-MS
(HP6890/HP5973N, Agilent) was performed on an Ultra 1 column (25 m, 0.32 mm I.D., 0.17 m thickness; Agilent) under
splitless conditions. Injector temperature was 275 C, gradient temperature was from 70 C hold for 1 min to 300 C/min
at a 30 C/min rate with a total analysis time of only 10 min.

*DAD1, 4.838 (2116 mAU,Apx) Ref=5.276 of 0524-015.D

*4-MEC (MthylEthylCathinone)

2.541
2.686
3.095

20

urine (20-fold diluted in blank plasma) by 150 L methanol

containing 1 mg/L methylmilnacipran as internal standard
(IS). After centrifugation, the supernatant was diluted 1:4
with water and 5 L were injected.
For LC-HR-MS/MS, fast and simple protein precipitation
was used with 100 L of urine mixed and shaken on a rotary
shaker with 500 L of acetonitrile for 2 min according to Wissenbach [12]. After centrifugation, 500 L were transferred
into a glass vial and evaporated to dryness under a gentle
stream of nitrogen at 50 C. The residue was dissolved in
50 L of a mixture of eluent A and eluent B (1:1; v/v).
was compared to 4-methyl-N-methyl-ephedrine, another

12.623

Atazanavir et
mtabolites

11.167
11.368

60

3.480

80

4.242

2.007

(c)

10

15

Figure 2. HPLC-UV-DAD chromatogram ( = 230 nm) of the patient

urine after acidic back-extraction.

UPLC-MS/MS was done on an Acquity Quattro Premier

apparatus (Waters, Guyancourt, France) with electrospray
ionization in positive mode (ESI+) and using multiple reaction monitoring (MRM) mode for quantication in plasma
and urine. The column was an Acquity UPLC BEH C18
1.7 m (50 2.1 mm I.D.) maintained at 40 C. Mobile phase
consisted of a mixture of 2 mm ammonium formate (containing 0.1% formic acid) and methanol under gradient
conditions from 80/20 to 10/90 in 2.5 min. Three transitions
were evaluated for 4-MEC (m/z 192 > 145; 192 > 159 cone
voltage 22 V Ecoll 20 eV for both and 192 > 174 cone
voltage 22 VEcoll 14 eV) and one transition for internal
standard (m/z 261.3 > 142.8; cone voltage 19 V; Ecoll 23 eV).
Calibration curve was tested between 10 and 1000 g/L and
3 controls were evaluated in triplicate on four different days
for validation process.
A ThermoFisher (TF, Dreieich, Germany) Accela LC system coupled to a TF Q-Exactive detector with heated
electrospray ionization (HESI)-II source was used for nal
identication of 4-MEC and metabolites. Chromatography
was performed with a TF Accucore PhenylHexyl column

*DAD1, 4.240 (123 mAU,Apx) Ref=3.016 of 0524-015.D

mAU

Norm

(a)

2000

(b)
100

1750
1500

80

1250
60

1000
750

40

500
20

250
0

0
225

Figure 3.

250

275

300

325

350

375

nm

min

225

250

275

300

325

UV spectra (210400 nm): (a) patient and reference 4-MEC and (b) supposed metabolite.

350

375

nm

Author's personal copy

122

A. Turcant et al.
2.6 m (100 2.1 mm I.D.) maintained at 35 C. The mobile
phase consisted of eluent A (water with 0.1% formic acid)
and eluent B (acetonitrile with 0.1% formic acid) with a ow
rate set to 0.5 mL/min and the gradient programmed as follows: 04.0 min 98 to 40% A, 47 min hold 10% A (total run
time per sample 10 min). The detailed HESI-II source conditions were described elsewhere [13].

Abundance
TIC: 1228008.D\data.ms
6.732

1.15e+07
1.1e+07

6,74

1.05e+07
1e+07
9500000
9000000
8500000
8000000
7500000

Results and discussion

6,30

7000000
6500000

7.905

6.304

6000000
5500000

7.725

5000000
5.813
6.053

4500000

5,81

4000000
3500000

6,53
7.853

6.532

3000000

6.987

2500000
7.553

2000000
1500000

7.438
b 7.38
8

1000000
500000
0

Time-->

4.50

5.00

5.50

6.00

6.50

7.00

7.50

Figure 4. GC-MS mode SCAN (50500 amu) of diluted 5-fold urine

sample after heptauorobutyric anhydride (HFBA) derivatization (a:
d5-MA; b: d5-MDMA).

The HPLC-UV analysis of the powder, presented as white ne

crystals in a plastic bag noted research chemical, showed
a near 100% purity of 4-MEC compared with reference pure
compound and expressed as a hydrochloride.
Urine drug testing was positive (threshold 500 g/L) for
amphetamine by IE and FPIA, but not for ecstasy and
IC tests were positive for amphetamine or doubtful for
ecstasy. Cannabis, cocaine, opiates, methadone and benzodiazepines were negative by FPIA. It can be noted that a
test with added 4-MEC (50 mg/L) on blank urine gave positive result with FPIA, but was uncertain with amphetamine
IE and negative with ecstasy IE and the two IC tests.
HPLC/DAD after acidic back-extraction exhibited different peaks at 230 nm wavelength detection in the urine
sample of the patient (Fig. 2). Besides atazanavir, an
antiretroviral drug, and its metabolites, 4-MEC was identied by both its retention time (RT = 4.84 min) and its UV

Figure 5. Mass spectra of heptauorobutyric anhydride (HFBA) derivatives (a) peak with RT 6.74 min corresponding to 4-MEC and (b) peak
with RT 6.30 min.

Author's personal copy

Acute combined poisoning with the new designer drug 4-MEC and GBL: A case report

Figure 6.

123

Mass spectra of heptauorobutyric anhydride (HFBA) derivatives (a) peak with RT 6.5 min and (b) peak with RT 5.51 min.

spectrum, compared with the reference 4-MEC (Fig. 3a).

Another peak of interest with the same spectrum as
that of the parent drug was observed at 3.48 min, suggesting a metabolite almost containing the keto function
associated with UV absorption around the 250260 nm.
It could be N-deethyl-4-MEC. Three other peaks with
identical UV proles (Fig. 3b), but without the characteristic band of 4-MEC, were seen at 2.55, 2.68, and
4.24 min. The extraction procedure indicated that these
products were basic drugs, probably other metabolites of
4-MEC. No other psychotropic drugs such as methylenedioxypyrovalerone (MDPV), methoxetamine, pentedrone,
2,5-dimethoxy-4-propylphenethylamine (2C-P) nor cardiovascular drugs were detected by our screening procedures.
The analysis of urine sample with the amphetamine GCMS procedure gave further information and completed these
hypotheses. Three peaks (RT 5.81, 6.53, 6.74 min) were
observed between the d5-MA and d5-MDMA retention times
(respectively 5.67 and 7.21 min) in selected ion monitoring mode and a 4th peak (RT 6.30 min) was observed after
repeating the injection in scan mode (Fig. 4). The mass spectrum of the main peak, identied as 4-MEC, was presented
in Fig. 5a with no visible molecular M+ ion at m/z 387, but
with a characteristic base peak at m/z 119, corresponding to
the 4-methylphenylcarboxy- moiety resulting from the rupture of the carbon bond in - position of the nitrogen atom

as described by Jankovics [14], and with a peak at m/z 268

resulting from the other part of the molecule containing the
HFB part. Another fragment could be observed at m/z 240,
i.e. loss of the ethyl part of the nitrogen atom. The peak
with RT equal to 6.30 min presented the same base peak at
m/z 119 with a second ion at m/z 240 but no other signicant
higher mass (Fig. 5b). This could correspond to the N-deethyl
HFB metabolite (theoretical molecular ion at m/z 359). Such
N-dealkylated metabolite was previously proposed by Meyer
et al. for mephedrone or 4-methyl-N-methylcathinone (4MMC) [1]. Based on this study, the peak observed at 6.50 min
(Fig. 6a) metabolite of mephedrone obtained by reduction of
the keto function resulted in the corresponding amino alcohol, which was available as pure substance. Three ions were
observed in this case with a delta mass of +14 compared to
the ephedrine analogue, i.e. 224 for 210, 329 for 315 and
371 for 357. A second spectrum (not shown) was observed
at approximately the same retention time with three main
ions at m/z 240, 268, and 372. For the ephedrine analogue,
a second spectrum was also observed with ions at m/z 210,
254, and 358. The difference of 30 observed for the rst ion
could be explained by the different substitution on the nitrogen atom as observed for the ethylamphetamine compared
with metamphetamine HFB derivatives. The two different
spectra observed in the patient urine could correspond to
mono-HFB or di-HFB derivatives as already described for

Author's personal copy

124
ephedrine and pseudoephedrine [15,16]. So, the peak at
6.53 min could be the 4-methyl-N-ethyl-norephedrine. This
substance, recently available as pure compound, was tested
under all our analytical conditions and it presented effectively the same RT and the same UV and MS spectra as that
of the compound detected in the patient urine. For the last
peak observed at 5.81 min (Fig. 6b), a mass shift of 28 was
observed for ions at m/z 344 and 240 compared to the amino
alcohol metabolite of 4-MEC. The fragment at m/z 317 could
be the O-HFB part after breaking of the - bond. So, this
metabolite was possibly 4-methyl-N-deethyl-norephedrine
or 1-[(4-methyl)-phenyl]-2-amino-propanol. The derivatization with pentauoropropionic anhydride led to the same
chromatographic prole with all spectra presenting a shift
of 50 uma (-CF2 - difference).
Finally, the phase-I metabolites suspected by HPLCUV/DAD and GC-MS were conrmed by LC-HR-MS/MS
(Fig. 7ad). The fragmentation of 4-MEC could be explain

A. Turcant et al.
by the loss of a water molecule (m/z 174.1277, C12 H16 N)
and then of a methyl group (m/z 159.1043, C11 H13 N) and
further loss of methylene group (m/z 145.0886, C10 H11 N).
The ion m/z 119.0857 resulted from a breakdown between
and -carbon leading to the 4-methylphenylcarboxy ion
(C8 H7 O) as seen upper in GC/MS. Detailed interpretation of
the fragmentation pathways as well as metabolism studies,
performed using this and other human urine samples as well
as pooled liver microsomes, were published elsewhere [17].
Thus, a metabolism scheme similar to mephedrone
could be concluded. Reduction of the keto group and Ndealkylation seemed to be two of the main routes for phase
I metabolism. These in vivo results were in correlation with
in vitro results described by Mueller and Rentsch for human
liver microsome incubations of 11 cathinones [17].
The UPLC-MS/MS method was developed with six-point
calibration (101000 g/L, r2 > 0.994, CV < 15%), limit of
quantication of 10 g/L, intraday and inter-day coefcient

Figure 7. High resolution MS/MS spectra of 4-MEC and its metabolites observed in urine; (a) 4-MEC; (b) 4-MEC-dihydro-; (c) 4-MEC-nor-;
(d) 4-MEC-nor-dihydro.

Author's personal copy

Acute combined poisoning with the new designer drug 4-MEC and GBL: A case report

Figure 7.

125

(Continued).

of variation below 7.5 and 7.9%. Typical chromatograms for

plasma and urine were presented in Fig. 8. Quantitative data
for 4-MEC showed plasma and urine levels of respectively
353 g/L and 100 mg/L.
Very few data were found on 4-MEC exposure with biological measurements. Recently, a case of intake of 5 g of NRG3
and 10 g of 4-MEC over 2 days was presented [18]. The purity
of the 4-MEC powder was 50%. The patient had hallucinogenic ush and tachycardia. The urine was collected more
than 48 hours after consumption and the 4-MEC concentration was only 200 g/L. In our case, the patient described
also a confused state with some hallucinogenic effects after
this rst intake of 4-MEC and urine levels were far higher but
collected earlier after intake. Other cases were described
by Gil et al. [9]. The rst one described blood and urine levels respectively of 152 and 122 g/L in a 30-year-old male
death in a car accident and the authors thought that he
was under the inuence of 4-MEC and alcohol (blood level:
1.2 g/L). The second case, also fatal, showed lower levels

respectively 152 and 122 g/L for blood and urine but the
death was explained by a high paramethoxyamphetamine
intake with blood level of 2.3 mg/L with little or no effect
of 4-MEC. The third one showed the lowest blood level
(46 g/L) but no clinical information was described for this
man arrested for suspicion of narcotics possession. Another
fatal poisoning case was described with a blood concentration of 1200 g/L and the authors described a possible
serotonin syndrome mechanism for the death with acute
circulatory and respiratory failure [19].
GHB levels, 300 and 1000 mg/L, respectively, for plasma
and urine, could explained the important observed symptoms such as unconsciousness and respiratory depression.
The rapid recovery under treatment in the emergency unit
was also in accordance to general data on GHB poisoning [20]. While the ingested GBL dose was not known, the
patient, after hospitalization, declared an over consumption of GBL compared previous intakes, probably under the
inuence of 4-MEC.

Author's personal copy

126

A. Turcant et al.

MDPV20130114_35
4-MECKOFFI 1
1.28
45256.29

100

MRM of 12 channels,ES+
192 > 145.1
1.101e+006

4-MEC

%
0

min

MDPV20130114_35

MRM of 12 channels,ES+
261.3 > 142.8
3.734e+005

IS
Methylminalcipram
1
2.04
14590.05

100
%
0

min
0.50

1.00

1.50

2.00

2.50

3.00

3.50

MDPV20130116_16
4-MEC KOFFI 1
1.27
84616.20

100

4.00

4.50

MRM of 12 channels,ES+
192 > 145.1
2.099e+006

4-MEC

%
0

min

MDPV20130116_16

MRM of 12 channels,ES+
261.3 > 142.8
5.341e+005

ISlcipram 1
Methylmina
2.04
20560.68

100
%
0

min
0.50

Figure 8.

1.00

1.50

2.00

2.50

3.00

3.50

4.00

4.50

UPLC-MS/MS chromatograms (top) plasma; (bottom) diluted 200-fold urine.

Conclusion
This case of 4-MEC exposure associated with GBL ingestion, documented with blood and urine concentrations,
was nally without clinical consequences for the patient.
However, the rapid admission in an emergency care unit
had probably preserved vital functions from effects of high
GHB levels. This case illustrated the potential risk of coconsumption of drugs of abuse with the risk of potentiation.
To our best knowledge, this is the rst case with identication of main metabolites of 4-MEC in human urine samples
with different analytical methods including high-resolution
mass spectrometry.

[2]

[3]
[4]

[5]

Disclosure of interest
[6]

The authors declare that they have no conicts of interest

concerning this article.
[7]

References
[8]
[1] Meyer MR, Wilhem J, Peters FT, Maurer HH. Beta-keto
amphetamines: studies on the metabolism of the designer

drug mephedrone and toxicological detection of mephedrone,

butylone, and methylone in urine using gas chromatographymass spectrometry. Anal Bioanal Chem 2010;397(3):
122533.
Wood DM, Dargan PI. Novel psychoactive substances: how to
understand the acute toxicity associated with the use of these
substances. Ther Drug Monit 2012;34(4):3637.
Meyer MR, Peters FT. Analytical toxicology of emerging drugs
of abuse an update. Ther Drug Monit 2012;34(6):61521.
Fornal E. Identication of substituted cathinones; 3,4methylenedioxy derivatives by high performance liquid
chromatography quadrupole time of ight mass spectrometry. J Pharm Biomed Anal 2013;8182:139.
Srensen LK. Determination of cathinones and related
ephedrines in forensic whole-blood samples by liquidchromatography-electrospray tandem mass spectrometry. J
Chromatogr B 2011;879:72736.
Pedersen AJ, Reitzel LA, Johansen SS, Linnet K. In vitro
metabolism studies on mephedrone and analysis of forensic
cases. Drug Test Anal 2013;5(6):4308.
Adamowicz P, Tokarczyk B, Stanaszek R, Slopianka M. Fatal
mephedrone intoxication a case report. J Anal Toxicol
2013;37(1):3742.
Zuba D, Adamowicz P, Byrska B. Detection of buphedrone in
biological and non-biological material two case reports. For
Sci Inter 2013;227:1520.

Author's personal copy

Acute combined poisoning with the new designer drug 4-MEC and GBL: A case report
[9] Gil D, Adamowicz P, Skulska A, Tokarczyk B, Stanaszek R. Analysis of 4-MEC in biological and non-biological material-three
case reports. For Sci Inter 2013;228:e115.
[10] Wood DM, Brailsford AD, Dargan PI. Acute toxicity and
withdrawal syndromes related to gamma-hydroxybutyrate
(GHB) and its analogues gamma-butyrolactone (GBL) and
1,4-butanediol (1,4-BD). Drug Test Anal 2011;3(78):
41725.
[11] Frec S, Bretaudeau-Deguigne M, Lelivre B, Boels D, Bruneau
C, Leborgne I, et al. Expositions rcratives de 8 patients aux
nouvelles drogues de synthse obtenues sur Internet: propos
de 3,4-methylenedioxypyrovalerone (MDPV) et de mthoxtamine (MXE). Ann Toxicol Anal 2013;25(2):4756.
[12] Wissenbach DK, Meyer MR, Remane D, Weber AA, Maurer HH.
Development of the rst metabolite-based LC-MSn urine drug
screening procedure exemplied for antidepressants. Anal
Bioanal Chem 2011;400(1):7988.
[13] Helfer AG, Turcant A, Boels D, Frec S, Lelivre B, Welter
J, et al. Elucidation of the metabolites of the novel psychoactive substance 4-methyl-N-ethyl-cathinone (4-MEC) in
human urine and pooled liver microsomes by GC-MS and LCHR-MS/MS techniques and of its detectability by GC/MS or
LC-MSn standard screening approaches Drug Test Anal 2014,
doi:10.1002/dta.1682. [Epub ahead of print].
[14] Jankovics P, Vradi A, Tlgyesi L, Lohner S, Nmeth-Palots J,
K
oszegi-Szalai H. Identication and characterization of the new
designer drug 4-methylethcathinone (4-MEC) and elaboration
of a novel liquid chromatography-tandem mass spectrometry

[15]

[16]

[17]

[18]

[19]

[20]

127

(LC-MS/MS) screening method for seven different methcathinone analogs. For Sci Inter 2011;210:21320.
Kankaanp A, Gunnar T, Ariniemi K, Lillsunde P, Mykknen
S, Seppl T. Single-step procedure for gas chromatographymass spectrometry screening and quantitative determination
of amphetamine-type stimulants and related drugs in blood,
serum, oral uid and urine samples. J Chromatogr B
2004;810:5768.
Marais AA, Laurens JB. Rapid GC-MS conrmation of
amphetamines in urine by extractive acylation. For Sci Inter
2009;183:7886.
Mueller DM, Rentsch KM. Generation of metabolites by
an automated online metabolism method using human
liver microsomes with subsequent identication by LC-MS
(n) and metabolism of 11 cathinones. Anal Bioanal Chem
2012;402(6):214151.
Knapp A, Humbert L, Etting I, Abe E, Garnier R, Alvarez JC.
Identication et dosage de la 4-MEC (4-mthyl-thylcathinone)
et de la MDPV (3,4-mthylnedioxypyrovalrone) dans
diffrents milieux: propos dun cas. Ann Tox Anal
2013;25(3):148.
Rojek S, Klys M, Maciow-Glab M, Kula K, Strona M. Cathinones derivatives-related deaths as exemplied by two fatal
cases involving methcathinone with 4-methylmetcathinone
and 4-methylethcathinone. Drug Test Anal 2014, doi:10.1002/
dta.1615. [Epub ahead of print].
Baselt RC. Disposition of toxic drugs and chemicals in man. 10th
ed. Seal Beach - California: Biomedical publications; 2011.