Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and other dimethoxyphenyl-N-[(2-methoxyphenyl) methyl]ethanamine derivatives on blotter paper

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DOI: 10.1093/jat/bkv073
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Abstract
In recent years, N-methoxybenzyl-methoxyphenylethylamine (NBOMe) derivatives, a class of designer hallucinogenic drugs, have become popular drugs of abuse. These drugs have been the cause of severe intoxications and even deaths. They act as 5-HT2A receptors agonists and have been reported to produce serotonin-like syndrome with bizarre behavior, severe agitation and seizures persisting for as long as 3 days. The most commonly reported derivatives are 25I-NBOMe, 25B-NBOMe and 25C-NBOMe, respectively 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl]ethanamine, N-(2-methoxybenzyl)-2,5-dimethoxy-4-bromophenethylamine and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine. Like many low dose hallucinogenic drugs these compounds are often sold on blotter paper. Three different types of commercially available blotter papers reported to contain NBOMe derivatives were obtained. These blotter papers were screened using Direct Analysis in Real Time AccuTOFTM mass spectrometry followed by confirmation and quantification by high-performance liquid chromatography triple quadrapole mass spectrometry. The major drug present on each of the three blotter products was different, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter papers were also found to have minute amounts of two or three NBOMe derivative impurities of 25H-NBOMe, 25I-NBOMe, 25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe.
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Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other
Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper
Justin L. Poklis1, Stephen A. Raso2, Kylie N. Alford2, Alphonse Poklis1,2,3 and Michelle R. Peace2*
1
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA,
2
Department of Forensic
Science, Virginia Commonwealth University, PO Box 843079, 1015 Floyd Avenue, Room 2015, Richmond 23284, VA, USA, and
3
Department of Pathology, Virginia Commonwealth University, Richmond, VA, USA
*Author to whom correspondence should be addressed. Email: mrpeace@vcu.edu
In recent years, N-methoxybenzyl-methoxyphenylethylamine (NBOMe)
derivatives, a class of designer hallucinogenic drugs, have become
popular drugs of abuse. These drugs have been the cause of severe
intoxications and even deaths. They act as 5-HT
2A
receptors agonists
and have been reported to produce serotonin-like syndrome with bi-
zarre behavior, severe agitation and seizures persisting for as long
as 3 days. The most commonly reported derivatives are 25I-NBOMe,
25B-NBOMe and 25C-NBOMe, respectively 2-(4-iodo-2,5-dimethoxy-
phenyl)-N-[(2-methoxyphenyl) methyl]ethanamine, N-(2-methoxyben-
zyl)-2,5-dimethoxy-4-bromophenethylamine and N-(2-methoxybenzyl)-
2,5-dimethoxy-4-chlorophenethylamine. Like many low dose halluci-
nogenic drugs these compounds are often sold on blotter paper.
Three different types of commercially available blotter papers report-
ed to contain NBOMe derivatives were obtained. These blotter pa-
pers were screened using Direct Analysis in Real Time AccuTOF
TM
mass spectrometry followed by confirmation and quantification by
high-performance liquid chromatography triple quadrapole mass
spectrometry. The major drug present on each of the three blotter
products was different, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe.
The blotter papers were also found to have minute amounts of two
or three NBOMe derivative impurities of 25H-NBOMe, 25I-NBOMe,
25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe.
Introduction
Recently, a new class of “2C” serotonin 5-HT
2A
receptor agonists
designer drugs, dimethoxyphenyl-N-[(2-methoxyphenyl) meth-
yl]ethanamine (NBOMe) derivatives have become easily obtain-
able over the Internet which has resulted in their abuse in the
USA, Europe and Asia (1). Stimulation of 5-HT
2A
receptors is re-
sponsible for the hallucinogenic effects of recreational drugs
such as lysergic acid diethylamide (LSD) and 1-(2,5-dimethoxy-
4-iodophenyl)-2-aminopropane (2). The terminology “2C” is an
acronym coined by Alexander Shulgin for the two carbon
atomsbetweenthebenzeneringandtheaminogrouponthe
perceptional distorting and/or hallucinogenic phenylethylamine
derivatives he synthesized (3,4). Several of these derivatives, in-
cluding 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)
methyl]ethanamine (25I-NBOMe) and N-(2-methoxybenzyl)-
2,5-dimethoxy-4-bromophenethylamine (25B-NBOMe) were
first synthesized by Ralf Heim at the Free University of Berlin as
part of a series of pharmacological tools to study the 5-HT
2A
re-
ceptor (57). Blotter papers containing 25I-NBOMe appeared
on the designer drug market beginning in 2011 (8)andsince
then numerous NBOMe derivatives have been identified in blot-
ter papers seized from the illicit drug market including:
2-(2,5-dimethoxy-4-methylphenyl )-N-(2-methoxybenzyl)ethan-
amine (25D-NBOMe), 2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-
methoxybenzyl)ethanamine (25E-NBOMe), 2-(2,5-dimethoxy-
3,4 dimethylphenyl)-N-(2-methoxybenzyl)ethanamine (25G-
NBOMe), N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophene-
thylamine (25C-NBOMe) and 2-(4-iodo-2,5-dimethoxyphenyl)-
N-[(2,3-methylenedioxyphenyl) methyl]ethanamine (25I-NBMD)
(911).
Several published abstracts and clinical case reports have de-
scribed signs and symptoms of 25I-NBOMe (1,8,1216),
25B-NBOMe (1720) and 25C-NBOMe (1821) intoxication.
These reports reveal NBOMe intoxicated patients are typically
young males, 1429 years old with clinical presentations of a
serotonin-like syndrome with bizarre behavior and severe agita-
tion and seizures persisting for as long as 3 days. 25I-NBOMe in-
toxication has been ruled the cause of death in two cases in
which the drug was detected in blood and urine (22).
Quantified distribution of 25I-NBOMe in body fluids and tissues
from a case of traumatic death has also been reported (23).
Deemed a hazard to public health and safety, the Drug
Enforcement Administration placed 25I-NBOMe, 25B-NBOMe
and 25C-NBOMe into Schedule 1 of the Controlled Substances
Act on 10 October 2013 (24).
Currently, the most widely abused of the many NBOMe deriva-
tives appears to be 25I-NBOMe (25 28) which is sold as a powder
or on blotter paper under the names 25I-NBOMe, “N-Bomb” and
“Smiles”. Anecdotal reports indicate the powder in doses of 50
250 mg may be administered sublingually, by insufflation or
applied to the buccal cavity. 25I-NBOMe blotter papers usually con-
tain higher doses of 500–800 mg, apparently due to low bioavail-
ability of the drug. Psychoactive drugs of abuse with very high
potency having effective doses in the microgram (mg) range are
often dissolved in a volatile solution and dropped or soaked on to
blotter paper. The paper is often perforated into tiny squares or
“tabs” which can be torn or cut apart and placed under the tongue
or swallowed. Historically, LSD has been distributed on blotter
paper with colorful and/or unique artwork which may serve as a
trademark in the illicit drug trade. NBOMe blotter paper is similarly
marked with identifying artwork and is often distributed and/or
sold on the street as “blotter acid”, in reference to LSD.
We present the analysis of three different types of commercial
available blotter papers reported to contain NBOMe derivatives.
The blotter papers were ordered over the Internet and received
before 25I-NBOMe, 25C-NBOMe or 25B-NBOMe were categorized
as Schedule I according to the Federal Controlled Substances Act
in November 2013. The blotters were advertised as containing
500 mg of either 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The
approximate price per “hit” of blotter paper was $5 USD.
These blotter papers arrived via the mail with a customs dec-
laration form attached to the front of the package claiming to
#The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Journal of Analytical Toxicology 2015;39:617–623
doi:10.1093/jat/bkv073 Special Issue
contain a “music CD”. Upon opening the package, a Christmas
music CD case was found that contained three different small
bags containing blotter paper (Figure 1). The first type of blotter
paper pictured part of a psychedelic sun and was labeled
“25C-NBOMe”; the second type of blotter paper pictured part
of a pyramid with an eye and was labeled “25I-NBOMe”; and
the third type of blotter paper pictured Felix the Cat and was la-
beled “25B-NBOMe”. These blotter papers were screened using
Direct Analysis in Real Time AccuTOF
TM
mass spectrometry
(DART-MS) followed by confirmation and quantification by high-
performance liquid chromatography triple quadrapole mass
spectrometry (HPLCMS-MS). The DART-MS method for the
rapid detection of NBOMe derivatives was performed on both
the blotter paper and the blotter papers dissolved in methanol.
Ten other NBOMe derivatives including: (E)-2-(4-iodo-2,5-dime-
thoxyphenyl)-N-(2-methoxybenzylidene)ethanamine (25I-NBOMe
imine), 25I-NBOMD, N-(2-fluorobenzyl)-2-(4-iodo-2,5-dimethox-
yphenyl)ethanamine (25I-NBF), 25G-NBOMe, 25D-NBOMe, 2-
(2,5-dimethoxyphenyl)-N-(2-methoxybenzylidene) ethanamine
(25H-NBOMe), (E)-2-(2,5-dimethoxyphenyl)-N-(2-methoxy-
benzylidene)ethanamine (25H-NBOMe imine), 25B-NBOMe,
25C-NBOMe and 2-(2,5-dimethoxy-4-(methylthio)phenyl)-
N-(2-methoxybenzyl)ethanamine (2CT-NBOMe) were also
evaluated in methanol. Confirmation and quantification were
performed on the methanol dissolved blotter papers using
HPLCMS-MS.
Methods
Reagents
The primary reference materials for 25I-NBOMe, 25I-NBOMe
imine, 25I-NBMD, 25I-NBF, 25G-NBOMe, 25D-NBOMe, 25H-
NBOMe, 25H-NBOMe imine, 25B-NBOMe, 25C-NBOMe and
2CT-NBOMe were purchased from Cayman Chemical Company
(Ann Arbor, MI, USA) as hydrochloride salts. Polyethylene glycol
(PEG) was purchased from ULTRA Inc. (North Kingstown, RI, USA).
Melting point tubes were obtained from Corning Incorporated
(Corning, NY, USA). Certified ACS ammonium acetate, formic
acid, HPLC grade methanol and deionized (DI) water were pur-
chased from Fisher Scientific (Hanover Park, IL, USA). Medical
grade nitrogen and helium were purchased from National
Welders Supply Company (Richmond, VA, USA). Blotter papers
containing NBOMe derivative were obtained through the
Internet at future-labs.eu.
Sample and reagent preparation
NBOMe derivative standards were individually prepared at 10, 25,
50 and 100 mg/mL. A 10 mg/mL NBOMe derivative mix standard
containing: 25I-NBOMe, 25I-NBOMe imine, 25I-NBMD, 25I-NBF,
25G-NBOMe, 25D-NBOMe, 25H-NBOMe, 25H-NBOMe imine,
25B-NBOMe and 25C-NBOMe was also prepared. A set of the
three different blotter paper products were each added to
10 mL of methanol which was then gently mixed to extract
the NBOMe derivatives. All stock standards were stored at
2208C until testing.
DART-MS analysis
The screening was performed using a DART-MS operated in
positive-ion mode and controlled by Mass Center software ver-
sion 1.3.4m (JEOL Inc. Tokyo, Japan). The Direct Analysis in
Real Time ion source had the helium gas flow rate at
2.0 L/min, gas heater temperature of 3008C, discharge electrode
needle at 4,000 V, Electrode 1 was set at 150 V and Electrode 2 at
250 V. The resolving power of the mass spectrometer was
6,000 full width at half maximum. Measurements were taken
Figure 1. NBOMe blotter papers as delivered.
618 Poklis et al.
with the ion guide peak voltage of 800 V, reflectron voltage of
900 V, Orifice 1 was operated at 3008C in 20, 60 or 90 V using
switching mode that created a single file for all three voltages,
Orifice 2 was set at 5 V and the ring lens was set at 3 V. The mea-
sured mass range was from 40 to 1,100 Da.
Sampling for the DART-MS was performed as previously de-
scribed by Steiner et al. (29). In brief, a mass spectrum of PEG
with average molecular weight 600 was obtained with each
data acquisition set as a reference standard to enable exact
mass measurements. The PEG and methanol standards contain-
ing the NBOMe derivatives were measured by dipping the closed
end of a cleaned glass melting point tube into the standard. The
blotter papers were analyzed by DART-MS using two different
sampling methods. The first analysis did not involve any sample
preparation. The blotter paper was held with a pair of forceps
and placed directly into the DART-MS gas stream. The second
analysis was performed by adding each blotter paper to 10 mL
of methanol and gently mixing for 1 h. The methanol solutions
were then sampled by dipping the closed end of a clean glass
melting point tube into the methanol containing the blotter
paper. The standards and samples were then moved back in
forth, or wanded, in to the DART gas stream. Each of the samples
or standards was wanded two times. The signal with the greatest
abundance was used for the data analysis. Data were created
using an averaged, background subtracted, centroided spectrum
that was calibrated to the PEG þH mass reference table. The
measured [MþH]
þ
spectra were compared with theoretical mas-
ses of each drug or fragment produced by in-source
collision-induced dissociation.
The evaluation of the NBOMe derivatives in methanol was
conducted over five separate days. The NBOMe derivative stan-
dards were analyzed for limit of detection (LOD), precision and
selectivity. The LOD of the DART-MS was evaluated using the
10, 25, 50 and 100 mg/mL of each NBOMe derivative standard.
They were analyzed ten times using different aliquots. The
intra- and interday precision for the mass accuracy was calcu-
lated from the analysis of five aliquots of each NBOMe deriva-
tive standard on three separate days for a total of 15 replicates.
The selectivity of the DART-MS was determined for the NBOMe
derivatives using the 10 mg/mL of NBOMe derivative mix stan-
dard. The acceptance criteria for each NBOMe derivative to be
considered above LOD were met if the measured mass
was within the instrument manufacturer’s specification
of +5.0 mmu of the theoretical mass. Selectivity was deter-
mined if the individual NBOMe derivatives could be distin-
guished in with the mixture.
HPLCMS-MS analysis
The confirmation and quantification of the NBOMe derivatives
on the blotter papers was performed using a modified previously
published HPLC-MS-MS method (30). In brief, the instrument
was an Applied Biosystems 3200 Q trap with a turbo V source
for TurbolonSpray attached to a Shimadzu SCL HPLC system con-
trolled by Analyst 1.4.2 software. Chromatographic separation
was performed on a Restek Allure Biphenyl 5 mm 1003.2 mm
column (Bellefonte, PA, USA). The mobile phase consisted of A:
DI Water with 10 mM ammonium acetate and 0.1% formic acid
and B: methanol. The following gradient was used: 0.00
1.0 min starting at 50% B with a linear gradient to 80% B, then
using linear gradient ending at 10.0 min to 70% B and finally re-
turning at 10.1 min to 50% B. The source temperature was set at
6508C and had a curtain gas flow rate of 30 mL/min. The ionspray
voltage was 5,000 V, with the ion source gases 1 and 2 at flow
rates of 30 mL/min. The acquisition mode used was multiple re-
action monitoring. The retention times (min), declustering po-
tential (V), transition ions (m/z) and corresponding collection
energies (eV) for all the compounds can be found in Table I.
The total run time for the analytical method was 13 min.
The evaluation of the HPLCMS-MS method was performed
over 3 days. A seven-point calibration curve containing 1, 2, 5,
10, 20, 50 and 100 ng/mL of the NBOMe derivatives in meth-
anol with 20 ng/mL added 25I-NBOMe-d3 was analyzed each
day. A linear regression of the ratio of the peak area counts
of NBOMe derivatives and the 25I-NBOMe-d3 internal standard
(ISTD) versus concentration was used to construct the calibra-
tions curves. Each sample batch also contained drug free con-
trol (negative control) with ISTD added, a double negative
control containing neither NBOMe derivatives nor ISTD, and
replicates (n¼3) of the following QC specimens prepared in
methanol containing the NBOMe derivatives: limit of quantifi-
cation quality control (LOQC), target concentration of
1.0 ng/mL; low control, target concentration of 3.0 ng/mL; me-
dium control, target concentration of 30 ng/mL; high control,
target concentration of 75 ng/mL. All QC samples were stored
at 2208C until testing. Stock standards were also evaluated for
stability by allowing aliquots of the stock standards to sit at
room temperature for 6 h. These aliquots and freshly prepared
stock standards were analyzed by the presented HPLC– MS-MS
method. The absolute areas of aliquots of NBOMe derivatives
kept at room temperature for 6 h were compared with the
freshly prepared stock standards. The HPLC –MS-MS analysis
of the blotter papers containing the NBOMe derivatives was
performed by adding each blotter paper to 10 mL of methanol
and gently mixing for 1 h. Samples were then further diluted to
the linear range of the assay and analyzed by the descried
HPLCMS-MS method.
Table I
The HPLC– MS-MS Acquisition Parameters
Designer drug RT (min) DP (V) Trans ions (m/z) CE (eV)
25H-NBOMe 7.45 45 302 .121 26
302 .91 55
25C-NBOMe 7.86 40 336 .121 25
336 .91 58
25I-NBF 7.86 60 416 .291 26
416 .109 65
25D-NBOMe 8.36 45 316 .121 26
316 .91 60
25B-NBOMe 8.77 45 380 .121 27
380 .91 65
2CT-NBOMe 8.86 45 348 .121 28
348 .91 60
25I-NBMD 9.64 60 442 .135 36
442 .77 90
25G-NBOMe 10.08 42 330 .121 27
330 .91 60
25I-NBOMe-d3 10.68 50 431 .124 30
431 .92 75
25I-NBOMe 10.77 55 428 .121 30
428 .91 70
Analysis of NBOMe Derivatives on Blotter Paper 619
Results
DART-MS analysis
[MþH]
þ
ions were produced at 20 V setting for Orifice 1. Less
abundant [MþH]
þ
ions were produced at 60 and 90 V. These
voltages produced greater abundance of product ions. All of
the analyzed NBOMe derivatives, with the exception of the
NBOMe imines, produced the same or similar product ions.
The 25H-NBOMe imine and 25I-NBOMe imine produced prod-
uct ions similar to each other through the same fragmentation
pattern (Figure 2). Each of the NBOMe derivatives analyzed pro-
duced [M þH]
þ
ions with mass accuracy of +5 mmu or better at
the administratively set LOD of 10 mg/mL. The measured mass
for all the NBOMe derivatives at 20, 60 and 90 V setting for
Orifice 1 were within +5.0 mmu of the theoretical mass for
both the inter- and intra-day precision. The selectivity of the
assay was determined by the 10 mg/mL NBOMe derivative mix
standard. All of the NBOMe derivatives present were distinguish-
able even though several of the NBOMe derivatives produced
product ions with the same structure and theoretical mass.
Eight of the 10 analyzed NBOMe derivatives produced product
ions that were unique to that NBOMe derivative (Table II).
The blotter papers and the blotter papers dissolved in methanol
were analyzed by the described DART-MS method. The most
abundant [M þH]
þ
ion peak produced with a 20 V setting was
within the acceptable mass accuracy of the NBOMe derivatives.
At the 60 and 90 V settings, the expected product ions were
Figure 2. Example of the fragmentation pattern for NBOMe derivatives using 25I-NBOMe and 25I-NBOMe imine.
Table II
DART-MS Produced Ions of the NBOMe Derivatives
Contributing NBOMe derivative(s) Fragment
formula
Calculated
mass
25I-NBMD C
18
H
20
NO
4
I 442.0515
25I-NBOMe C
18
H
22
NO
3
I 428.0723
25I-NBOMe imine C
18
H
20
NO
3
I 426.0566
25I-NBF C17H
19
NO
2
FI 416.0523
25B-NBOMe C
18
H
22
BrNO
3
380.0861
25C-NBOMe C
18
H
22
ClNO
3
336.1366
25G-NBOMe C
20
H
27
NO
3
330.2069
25D-NBOMe C
19
H
25
NO
3
316.1913
25H-NBOMe C
18
H
23
NO
3
302.1756
25B-NBOMe, 25I-NBOMe C
18
H
24
NO
3
302.1756
25H-NBOMe imine C
18
H
21
NO
3
300.16
25I-NBOMe imine C
18
H
22
NO
3
300.16
25I-NBF, 25I-NBMD, 25I-NBOMe, 25I-NBOMe imine C
10
H
12
O
2
I 290.9882
25B-NBOMe C
17
H
21
NO
2
F 290.1556
25C-NBOMe C
10
H
12
BrO
2
243.002
25G-NBOMe C
10
H
12
ClO
2
199.0526
25D-NBOMe C
12
H
17
O
2
193.1229
25H-NBOMe imine, 25I-NBF, 25H-NBOMe, 25I-NBOMe,
25I-NBOMe imine
C11
H
15
O
2
179.1072
25H-NBOMe imine C
10
H
13
O
2
165.0916
25I-NBMD C
9
H
11
O
2
150.0681
25H-NBOMe imine, 25I-NBOMe imine C
8
H
9
O
2
137.0603
25I-NBMD C
8
H
7
O
2
135.0446
25C-NBOMe, 25B-NBOMe, 25G-NBOMe,
25D-NBOMe,25H-NBOMe, 25I-NBOMe
C
8
H
9
O 121.0653
25I-NBF C
7
H
6
F 109.0454
25H-NBOMe imine, 25I-NBOMe imine C
7
H
7
O 107.0497
25C-NBOMe, 25B-NBOMe, 25H-NBOMe, 25D-NBOMe,
25G-NBOMe, 25I-NBOMe
C
7
H
7
91.0548
620 Poklis et al.
detected. As advertised, the blotter paper picturing part of a psy-
chedelic sun was found to contain 25C-NBOMe; the second type
of blotter paper picturing the pyramid with an eye was found to
contain 25I-NBOMe; and the third type of blotter picturing Felix
the Cat was found to contain 25B-NBOMe. These blotter papers
were also determined to contain other less abundant NBOMe de-
rivatives (Figure 3).
HPLCMS-MS analysis
The linear regression correlation coefficients (r
2
)forallthe
NBOMe calibration curves yielded the least fit mean r
2
of 0.9997
or better. The lower limit of quantification (LOQ) and lower LOD
was administratively set at 1 ng/mL. LOQC samples were used to
verify that the LOQ was within +10% of the target value and had
a response at least 10 times greater than the signal-to-noise ratio
of the methanol negative control. The precision and accuracy/
bias for all nine NBOMe derivatives was determined to have
%CVs that did not exceed a 7% and were within 94 104% of
their expected values for all QC samples. For the assessment
of carryover, none of the NBOMe derivatives were detected
in the negative controls that were immediately injected after
the 100 ng/mL calibrator. The absolute percent difference of
the stock standards samples used to assess the stability of the
NBOMe derivatives and the ISTD, 25I-NBOMe-d3 were within
26 and 5% of the expected values. Analysis of the methanol con-
taining the blotter papers confirmed the DART-MS results. The
HPLCMS-MS analysis allowed for the quantitation of the detect-
ed NBOMe derivatives on each of the blotter papers (Table III).
Discussion
Several NBOMe derivatives including 25D-NBOMe, 25E-NBOMe,
25G-NBOMe, 25C-NBOMe, 25I-NBOMe and 25C-NBOMe mixed
with 25D-NBOMe have been reported as detected on blotter
papers using liquid chromatographic mass spectrometry,
Fourier transform spectroscopy, nuclear magnetic resonance
spectroscopy and/or gas chromatography mass spectrometry
methods (9,10,23). In contrast to these previously reported
NBOMe derivatives on blotter paper, using the DART-MS method
required no solvents, extractions, or sample preparation. The
blotter paper was held with a pair of forceps and placed directly
into the DART-MS gas stream and yielded spectra information in a
Figure 3. Blotter paper DART-MS spectra at of 20 V setting for Orifice 1. This figure is available in black and white in print and in color at JAT online.
Analysis of NBOMe Derivatives on Blotter Paper 621
few seconds. Unlike previously reported blotter paper analyses,
the presented DART-MS method allows for rapid identification
of the major NBOMe derivative. The DART-MS analysis of the
three different blotter papers resulted in the detection of a
major drug present, either 25I-NBOMe, 25C-NBOMe or
25B-NBOMe and minute amounts of two or three NBOMe deriv-
atives as impurities, 25H-NBOMe, 25I-NBOMe, 25C-NBOMe,
25B-NBOMe and/or 25D-NBOMe. Previously published analyses
of blotter papers containing NBOMe derivatives have not report-
ed detecting trace amounts of an NBOMe derivative with a much
larger concentration of a single NBOMe derivative. These impu-
rities detected on the blotter papers are likely a result of the syn-
thesis and/or contamination post synthesis, possibly during the
production of the blotter papers. The identification of these
types of impurities help explain urines values reported in the lit-
erature where a large concentration of 25I-NBOMe is reported
with lower concentrations of 25C-NBOMe and/or 25H-NBOMe
(8,30) even though neither 25C-NBOMe nor 25H-NBOMe ap-
pear to be metabolites of 25I-NBOMe.
The HPLC– MS-MS analysis of the blotter papers confirmed the
DART-MS results. Previously published analyses of blotter papers
containing NBOMe derivatives have not reported concentrations
or accuracy of the vendor-advertised concentrations. The adver-
tised concentration of each of the blotter papers was 500 mgof
25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter papers
were correctly labeled as to their major NBOMe derivative. The
blotter paper that pictured part of a psychedelic sun was labeled
“25C-NBOMe”. It was determined to be correctly labeled with the
drug, containing 102% of the labeled dose and 3.3% NBOMe deriv-
ative impurities. The blotter paper that pictured a pyramid withan
eye was labeled “25I-NBOMe”. It was determined to be correctly
labeled with the drug, containing 108% of the labeled dose and
8.0% NBOMe derivative impurities. The blotter paper pictured
Felix the Cat and was labeled “25B-NBOMe”. It was determined
to be correctly labeled with the drug, containing 300% of the
labeled dose and 2.2% NBOMe derivative impurities. The discrep-
ancy in the calculated concentration versus the advertised con-
centrations of Felix the Cat blotter paper indicates that the
advertised concentration may not be accurate and, in some
cases, the concentration of the NBOMe derivative may be several
times greater than expected.
Conclusion
Three different types of commercially available blotter papers
were analyzed using a DART-MS and confirmed and quantitated
by HPLC– MS-MS. Both methods used were able to detect and dif-
ferentiate between multiple NBOMe derivatives on the same blot-
ter paper. Each blotter paper yielded a different major NBOMe
derivative, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter
papers were also found to contain minute amounts of two or
three NBOMe derivative impurities including 25H-NBOMe,
25I-NBOMe, 25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe.
The identification of these impurities may help explain reports
of urine analyses which identified a large concentration of
25I-NBOMe and a much lower concentration of 25C-NBOMe
and/or 25H-NBOMe. Neither 25C-NBOMe nor 25H-NBOMe
appears to be metabolites of 25I-NBOMe. The discrepancy in
the calculated concentration versus the advertised concentrations
of Felix the Cat blotter paper indicates that the advertised concen-
tration may not be accurate and, in some cases, the concentration
of the NBOMe derivative may be several times greater than
expected.
Acknowledgements
The authors thank Dr Robert Cody for his helpful suggestions to
improve this manuscript.
Funding
This work was supported in part by the National Institutes of
Health (P30DA033934).
Conflict of interest
None declared.
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Analysis of NBOMe Derivatives on Blotter Paper 623
  • ... -human dried blood spots to examine of long-term stability, -human whole blood to evaluate instability, -pocrine and human liver microsomes and blood samples to identify metabolites, -human serum and urine samples to identify metabolites , -human urine and hair samples in rats, -human heart blood and urine specimens, -human whole blood, (15,20,49,51,54,60,62) (27) ...
    Article
    NBOMes are N-benzylmethoxy derivatives of the 2C family compounds with N-2-methoxy-benzyl moiety substituted by the methoxy group at the 2- and 5- position and the halogen group at the 4- position of the phenyl ring. These substances are a new class of potent serotonin 5-HT2A receptor agonist hallucinogens with potential harmful effects. The substitution with halogen of the already psychoactive phenethylamine produces a derivative (2C-I) with increased hallucinogenic effects. This class of hallucinogens have chemical structures very similar to natural hallucinogenic alkaloid mescaline and are sold mainly via internet as a ‘legal’ alternative to other hallucinogenic drug- lysergic acid diethylamide (LSD). 25I-NBOMe is the first synthesized and one of the most common compound from NBOMes. Knowledge of pharmacological properties of 25I-NBOMe is very limited so far. There are only a few in vivo and in vitro so far published studies. The behavioural experiments are mainly related with the hallucinogenic effect of 25I-NBOMe while the in vitro studies concerning mainly the affinity for 5-HT2A receptors. The 25I-NBOMe Critical Review 2016 reported 51 non-fatal intoxications and 21 deaths associated with 25I-NBOMe across Europe. Case reports describe various toxic effects of 25I-NBOMe usage including tachycardia, hypertension, hallucinations, rhabdomyolysis, acute kidney injury and death. The growing number of fatal and non-fatal intoxication cases indicates that 25I-NBOMe should be considered as a serious danger to public health. This review aims to present the current state of knowledge on pharmacological effects and chemical properties of 25I-NBOMe, and to describe reported clinical cases and analytical methods available for identification of this agent in biological material.
  • ... NBOMes produce an array of adverse effects (Hill et al., 2013;Rose et al., 2013;Bersani et al., 2014;EMCDDA, 2014;Forrester, 2014;Grautoff and Kähler, 2014;Lawn et al., 2014;Stellpflug et al., 2014;Suzuki et al., 2014;Tang et al., 2014;World Health Organization, 2014a,b;Hieger et al., 2015;Nikolaou et al., 2015;Poklis et al., 2015b;Srisuma et al., 2015;Wood et al., 2015;Gee et al., 2016;Kristofic et al., 2016;Hermanns-Clausen et al., 2017;Humston et al., 2017;Madsen et al., 2017;Rajotte et al., 2017;Schetz et al., 2017;Wiergowski et al., 2017;Zygowiec et al., 2017;Marchi et al., 2019;Erowid.org); for comprehensive reviews see Suzuki et al., 2015;Halberstadt, 2017). ...
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    Full-text available
    Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of non-fatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.
  • ... The amount of NBOMes on a single trip ranges from approximately 500 to 1500 µg, while the single effective dose for an unexperienced user is around 100 µg. [24] Coelho et al. used direct ATR-FTIR spectroscopy for rapid detection of NBOMes on blotter papers, which required no sample preparation and was directly applied on blotter papers. The data indicated a heterogeneous distribution of the NBOMes. ...
    Article
    Due to much lower production costs but similar effects as lysergic acid diethylamide (LSD), phenethylamine derivatives are sold as a cheaper replacement or deceptively as LSD itself. These potent hallucinogenic substances can lead to severe intoxication, thus a more profound understanding of their use is required. This includes the elucidation of the manufacturing processes for the commonly used blotter papers and the assessment of the risk of overdosing because of a heterogeneous distribution on the blotter papers. Besides the rapid detection of the analytes, the manufacturing process was elucidated via three different imaging techniques and liquid chromatography‐mass spectrometry (LC‐MS). A blotter paper sample, containing the two hallucinogenic phenethylamine derivatives 25I‐NBOMe and 25C‐NBOMe, was analyzed via complementary techniques such as micro x‐ray fluorescence (μXRF), laser ablation (LA)‐inductively coupled plasma‐optical emission spectroscopy (ICP‐OES), matrix assisted laser desorption ionization (MALDI)‐MS and with LC‐MS after extraction. Using the signal from chlorine and iodine within the compounds, μXRF proved to be the fastest, cheapest and easiest method for identification, requiring no sample preparation at all. LA‐ICP‐OES provided three‐dimensional information of the elements in the blotter paper. These results helped to confirm the assumption that manufacturers spray the compounds onto the paper. Whereas μXRF and LA‐ICP‐OES detected signals for chlorine and iodine, MALDI‐MS‐imaging showed the molecular distribution of both analytes. LC‐MS analyses as a complementary method support the imaging results. Quantitative results for different drug hotspots revealed a heterogeneous distribution of the drugs on the blotter paper implying an inherent risk of overdosing for the consumers.
  • ... In 2010 the first reports of online vendors distributing compounds from this class as designer drugs or New Psychoactive Substances (NPS) emerged, with 25I-NBOMe and 25B-NBOMe being the first compounds from this class to appear. 25 Before long, accounts of toxicity and lethal overdoses from these drugs appeared, which resulted in the scheduling of these compounds by the DEA in November 2013. ...
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    N-Benzylphenethylamines, commonly known as NBOMes, are synthetic psychedelic compounds derived from the phenethylamine class of psychedelics (2C-X compounds), which originally have been derived from the naturally occurring alkaloid mescaline. Analogously to their parent compounds and other classical psychedelics, such as psilocybin and LSD, NBOMes are believed to exert their main pharmacological effects through activation of serotonin 2A (5-HT2A) receptors. Since their introduction as New Psychoactive Substances (NPSs) in 2010, NBOMes have been widely used for recreational purposes; this has resulted in numerous cases of acute toxicity, sometimes with lethal outcomes, leadingto the classification of several NBOMes as Schedule I substances, in 2013. However, in addition to their recreational use, the NBOMe class has yielded several important biochemical tools, including [11C]Cimbi-36, which is now being used in positron emission tomography (PET) studies of the 5-HT2A and 5-HT2C receptors in the mammalian brain, and 25CN-NBOH, one of the most selective 5-HT2A receptor agonists developed to date. In this review, the history, chemistry and structure-activity relationships, ADME properties and safety profiles of NBOMes will be outlined and discussed.
  • ... As DOB, DOC is an amphetamine designer drug that has similar effects to other amphetamines, including tachycardia, hypertension, anion gap acidosis, rhabdomyolysis, tremors, and seizures [15]. As shown in Table 2 The NBOMes, which are a generic denomination for phenethylamines presenting a 2-methoxybenzyl group replacing a hydrogen on the amine, were first detected in 2014 and have been attracting attention from medical and legal authorities [16]. Blotter papers and powders containing these substances were first reported in Poland in 2011 [17] but they were also detected in the USA [18]. ...
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    Designer drugs or new psychoactive substances (NPS) are a heterogeneous group of substances obtained through the modification of chemical structure of some natural products or drugs. NPS illegally commercialized in blotter papers mimicking the most common form of LSD consumption, with a great variability of colours and symbols, have largely increased worldwide, including in Brazil, becoming an important emerging public health issue. In this study, we have evaluated the presence and profile of NPS in blotters seized in the State of Santa Catarina, Brazil, over the period of 2011 to 2017. The state government criminal forensics staff has performed gas chromatography-mass spectrometer (GC-MS) analyses in order to determine the chemical composition of the blotters. During the evaluated period, there was a considerable increase in the seizing of blotters events, from 87 in 2011, to 301 in 2016 and reaching 277 in 2017. There was also an increase in the number of blotters seized per event. Interestingly, while in 2011, 100% of blotters contained LSD, this number decreased to 0,1% in 2014, and achieved 17,6% in 2017, when up to 25 different substances were detected in blotters seized. Drugs such as DOx, NBOMe, fentanyl, mescaline derivatives, triptamines, cathinones, and synthetic cannabinoids were detected and became the major substances found in blotters. In some cases, more than one substance was found in the same blotter, characterizing a new mixture scenario. The presence of several new psychoactive substances in blotters is a reality in forensic toxicology. In Brazil, it might be related to the fact that most of these substances were not considered illegal by Brazilian legislation by the time they emerged.
  • ... The selectivity of the proposed method was examined by testing the possibility of interference of LSD with the determination of NBOMEs, as NBOMes are commonly sold on blotter papers represented as LSD. 22 As seen in Figure 3, the LSD did not interfere with any of the four NBOMe derivatives, as it eluted early at the beginning of the chromatographic run with retention times (t R ) = 2.77 min in HPLC-DAD ( Figure 3A) and 2.78 min in HPLC-AD ( Figure 3B). The resolution (R s ) between the LSD peak and the next peak in the chromatogram (25F-NBOMe, 2a) is equivalent to 3.73, which proves the good selectivity and the successfulness of the proposed protocol. ...
    Article
    The emergence of a new class of novel psychoactive substances, N-benzyl-substituted phenethylamine derivatives so-called “NBOMes” or “Smiles”, in the recreational drug market has forced the development of new sensitive analytical methodologies for their detection and quantitation. NBOMes’ hallucinogenic effects mimic those of the illegal psychedelic drug lysergic acid diethylamide (LSD) and are typically sold as LSD on blotter papers, resulting in a remarkable number of fatalities worldwide. In this article, four halide derivatives of NBOMe, namely, 2-(4-fluoro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, and 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethan-1-amine, were detected and quantified simultaneously using a high-performance liquid chromatographic method, and two detection systems were compared: photodiode array detection (detection system I) and amperometric detection via a commercially available impinging jet flow-cell system incorporating embedded graphite screen-printed macroelectrodes (detection system II). Under optimized experimental conditions, linear calibration plots were obtained in the concentration range of 10–300 and 20–300 μg mL–1, for detection systems I and II, respectively. Detection limit (limit of detection) values were between 4.6–6.7 and 9.7–18 μg mL–1, for detection systems I and II, respectively. Both detectors were employed for the analysis of the four NBOMe derivatives in the bulk form, in the presence of LSD and adulterants commonly found in street samples (e.g. paracetamol, caffeine, and benzocaine). Furthermore, the method was applied for the analysis of simulated blotter papers, and the obtained percentage recoveries were satisfactory, emphasizing its advantageous applicability for the routine analysis of NBOMes in forensic laboratories.
  • Article
    Additive manufacturing (AM/3D printing) is an emerging technology of vast applicability receiving significant interest in a plethora of industrial domains and scientific research since it allows the rapid translation of designs produced via computer software, into AM/3D printed objects. To date, AM/3D printed devices have been examined for their utilisation as convenient and cost-effective tools towards the detection and quantification of prevalent drugs of abuse. Herein, a novel AM/3D printed wall-jet flow cell was fabricated specifically for employment in high performance liquid chromatography-amperometric detection (HPLC-AD) of various analytes (New Psychoactive Substances). Five sensing AM/3D printed platforms were investigated, utilising different working electrodes, namely; screen-printed graphite electrodes (SPEs), AM/3D Proto-Pasta, AM/3D Black Magic, graphite sheet and AM/3D printed nanographite (NG) /polylactic acid (PLA)) towards the detection of New Psychoactive Substances. The flow cell was also optimised with respect to the cell geometry demonstrating significant benefits such as simple production and operation and the ability to tailor the platform to a variety of working electrodes. The AM/3D printed sensing platforms were characterised towards the (electro)analytical detection of four N-benzylmethoxy- derivatives: 25F-NBOMe, 25C-NBOMe, 25B-NBOMe and 25I-NBOMe. Furthermore, the (electro)analytical performance of the flow cells were compared with the findings in our previous work comprising of a commercially available impinging jet flow cell. The SPEs and the graphite sheet were found to demonstrate superior electrochemical (analytical) sensitivity and higher reproducibility towards the quantification of the drugs in question, followed by the NG/PLA AM, Proto-Pasta and the Black Magic. The working electrodes that exhibited (electro)analytical responses were employed for the analysis of NBOMe derivatives in three simulated blotter papers.
  • Article
    Herein, we present the synthesis, characterization and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I‐NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5‐HT 2A receptor antibody. In the presence of 25I‐NBOMe the capping antibody is displaced leading to pore opening and rhodamine B release. This delivery was ascribed to 5‐HT 2A receptor antibody detachment from the surface due to its stronger coordination with 25I‐NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 µM) and selective recognition of the 25I‐NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I‐NBOMe illicit drug in artificial saliva and in sweets.
  • Article
    Rationale: The halogenated derivatives of N-(2-methoxy)benzyl-2,5-dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo-analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was to determine the role of the electron-donating groups (halogen and dimethoxy) on the pathway of decomposition for the distonic molecular radical cation in the EI-MS of the trifluoroacetamide (TFA) derivatives. Methods: The systematic removal of substituents from the 4-halogenated-2,5-dimethoxy-phenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzyl substituted analogs (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared, derivatized and analyzed via GC/EI-MS. Results: The analogues yield two unique radical cation fragments from the decomposition of the common distonic molecular radical cation. The substituted phenylethene radical cation (m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation (m/z 263) is the base peak or second most abundant ion in the 2- and 3MMPEADMB isomers. However, the 2- and 3-methoxyphenylethene radical cation (m/z 134) is among the five most abundant ions for each of these twelve isomers. Only one isomer in the PEADMB series yields the corresponding unsubstituted phenylethene radical cation at m/z 104. Conclusions: The decomposition of the hydrogen rearranged distonic molecular radical cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the less electron rich phenethyl aromatic rings. The addition of electron-donating groups to the aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the decomposition of the common distonic molecular radical cation to favor the formation of the electron-rich substituted phenylethene radical cation.
  • Article
    Purpose Toxicokinetic studies are essential in clinical and forensic toxicology to understand drug–drug interactions, influence of individual polymorphisms, and elimination routes, as well as to evaluate targets for toxicological screening procedures. N-(2-Methoxybenzyl)-substituted phenethylamines (NBOMe analogues) intake has been associated with severe adverse reactions including deaths. 1-(1-Benzofuran-5-yl)-N-[(2-methoxyphenyl)methyl]propan-2-amine (5-APB-NBOMe), 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b′]difuran-4-yl)-N-[(5-chloro-2-ethoxyphenyl)methyl]ethan-1-amine (2C-B-FLY-NB2EtO5Cl), and 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b′]difuran-4-yl)-N-[(2-methoxyphenyl)methyl]ethan-1-amine (2C-B-FLY-NBOMe) are three emerging NBOMe analogues, which have encountered on the drugs of abuse market. So far, their toxicokinetic data are completely unexplored. Methods The study included mass spectrometry-based identification of phase I and II metabolites following exposure to the terminally differentiated human hepatocellular carcinoma cells (HepaRG). The determination of enzymes involved in the major phase I/II metabolic steps and determination of plasma protein binding (PPB) were done. Finally, the evaluation of the toxicological detectability by different hyphenated mass spectrometry techniques in standard urine screening approaches (SUSAs) was investigated. Results The compounds were extensively metabolized in HepaRG cells mainly via O-dealkylation, hydroxylation, glucuronidation, and combinations thereof. CYP1A2, 2D6, 2C8, 2C19, and 3A4, were involved in the initial reactions of all investigated compounds. Glucuronidation of the phase I metabolites—when observed—was mainly catalyzed by UGT1A9. The PPB of all compounds was determined to be > 85%. Only the high-resolution mass spectrometry-based SUSA allowed detection of all compounds in rat urine, but only via metabolites. Conclusions The toxicokinetic data provided by this study will help forensic and clinical toxicologists to reliably identify these substances in case of abuse and/or intoxication and will allow them a thorough risk assessment.
  • Article
    The Administrator of the Drug Enforcement Administration is issuing this final order extending the temporary schedule I status for three synthetic phenethylamines into the Controlled Substances Act pursuant to the temporary scheduling provisions of the Act. The substances are: 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe; 2C-I-NBOMe; 25I; Cimbi-5), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25C-NBOMe; 2C-C-NBOMe; 25C; Cimbi-82), and 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe; 2C-B-NBOMe; 25B; Cimbi-36) [hereinafter 25I-NBOMe, 2C-NBOMe, and 25-NBOMe, respectively]. The initial temporary scheduling was based on a finding by the Deputy Administrator that the placement of these synthetic phenethylamines and their optical, positional, and geometric isomers, salts, and salts of isomers into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. The current final order temporarily placing 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe in schedule I is due to expire on November 14, 2015. This final order will extend the temporary scheduling of 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe for one year, or until the permanent scheduling action for these three substances is completed, whichever occurs first. As a result of this order, the full effect of the Controlled Substances Act and its implementing regulations, including criminal, civil and administrative penalties, sanctions, and regulatory controls of schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic phenethylamines.
  • Article
    The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily schedule three synthetic cathinones under the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). The substances are 4-methyl-N-methylcathinone (mephedrone), 3,4-methylenedioxy-N-methylcathinone (methylone), and 3,4-methylenedioxypyrovalerone (MDPV). This action is based on a finding by the Administrator that the placement of these synthetic cathinones and their salts, isomers, and salts of isomers into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety. As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil and administrative penalties, sanctions and regulatory controls of Schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cathinones.
  • Article
    A new class of synthetic hallucinogens called NBOMe has emerged as drugs of abuse. Our aim was to conduct a systematic review of published reports of toxicities associated with NBOMe ingestion.Methods We searched the PubMed for relevant English language citations that described adverse effects from analytically confirmed human NBOMe ingestion. Demographic and clinical data were extracted.ResultsTen citations met criteria for inclusion, representing 20 individual patients. 25I-NBOMe was the most common analog identified, followed by 25B-NBOMe and 25C-NBOMe. Fatalities were reported in 3 (15%) cases. Seven (35%) were discharged after a period of observation, while 8 (40.0%) required admission to an intensive care unit. The most common adverse effects were agitation (85.0%), tachycardia (85.0%), and hypertension (65.0%). Seizures were reported in 8 (40.0%) patients. The most common laboratory abnormalities were elevated creatine kinase (45.0%), leukocytosis (25.0%), and hyperglycemia (20.0%).ConclusionNBOMe ingestion is associated with severe adverse effects. Clinicians need to have a high index of suspicion for NBOMe ingestion in patients reporting the recent use of hallucinogens.
  • Article
    Introduction The NBOMes (N-benzyl-oxy-methyl derivatives of known 2C phenylethylamines) are a new and growing class of potent synthetic stimulants. Case reports provide the bulk of available safety and clinical data for clinicians. We report two cases of NBOMe intoxication with 25C-NBOMe (the first lab-confirmed US case) and 25B-NBOMe, respectively, both confirmed via triple quadrapole mass spectrometry. Case Reports Case 1: A 16-year-old girl had a generalized seizure after reported use of 25I-NBOMe. She presented with altered mental status, lower extremity rigidity, and elevated CPK (6042 U/L). Despite treatment with benzodiazepines, her lower extremity rigidity persisted and CPK peaked at 47,906 U/L. She was discharged on hospital day 8. Serum and urine specimens confirmed presence of 25C-NBOMe. Case 2: A 15-year-old boy developed bizarre behavior after reported use of 25I-NBOMe. In the ED, he had two generalized seizures and persistent muscle rigidity. CPK peaked at 429 U/L. Seizures were managed with benzodiazepines, and he was discharged within 24 h. Serum specimens revealed 25B-NBOMe. Discussion NBOMes are amphetamine derivatives and highly potent 5-HT2A receptor agonists. Clinical manifestations are a product of enhanced central sympathetic and serotonergic tone. We report two cases of NBOMe intoxication in patients who believed they used 25I-NBOME, while lab confirmation proved otherwise. Whether unique clinical manifestations are specific to the NBOMe variant, dose, route of administration, or other factors is unknown. Laboratory confirmation may play a role in identifying unexpected NBOMe variants, while contributing to the epidemiologic data on these novel substances.
  • Article
    Full-text available
    Abstract A new class of synthetic hallucinogens called NBOMe has emerged, and reports of adverse effects are beginning to appear. We report on a case of a suicide attempt after LSD ingestion which was analytically determined to be 25I-NBOMe instead. Clinicians need to have a high index of suspicion for possible NBOMe ingestion in patients reporting the recent use of LSD or other hallucinogens.
  • Article
    As potent serotonin (5-HT2A) receptor agonists, the NBOMe class of drugs including 25B-, 25C-, 25D-, 25H-, 25I- and 25T2-NBOMe is frequently abused due to the intense hallucinations that they induce. From the limited literature available, the concentration of these NBOMe compounds reported in postmortem cases is exceedingly low. In most instances, published concentrations are <0.50 ng/mL. Therefore, the need for a sensitive, rapid and comprehensive analytical method for the quantification of these compounds was evident. In addition to the more publicized analog 25I-NBOMe, evaluation of 25B-, 25C-, 25D-, 25H and 25T2- in whole blood, plasma and urine was conducted. This publication presents the data obtained from the validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of these six NBOMe analogs. The method utilizes ultra-performance liquid chromatography technology for the separation followed by positive electrospray ionization of each analog. Limits of quantification for these analogs ranged from 0.01 to 0.02 ng/mL (10-20 pg/mL) with typical linear dynamic ranges of 0.01-20 ng/mL. Data for recovery, intraday control accuracy and precision, matrix effects, ion suppression/enhancement and analyte stability are included. Validation was completed in whole blood, plasma and urine. Short run times and high sensitivity afforded by this newly validated analytical method that allows for the detection of these six analogs in the most common toxicological matrices and can be applied to both ante- and postmortem specimens.
  • Article
    ABSTRACT Use of 2-methoxybenzyl analogues of 2C-X phenethylamines (NBOMe) is increasing in the United States. Twenty-five NBOMe exposures reported to Texas poison centers during 2012-2013 were identified; 76% involved 25I-NBOMe, 12% 25C-NBOMe, and 12% an unknown NBOMe. Eighty-eight percent of the patients were male; the mean age was 17 years (range 14-25 years). The exposure route was 72% ingestion alone, 12% inhalation alone, 4% ingestion and inhalation, and 12% unknown route. The most common clinical effects were tachycardia (52%), agitation (48%), hallucinations (32%), hypertension (32%), confusion (24%), and mydriasis (20%). Two patients died.