bath salt-type aminoketone designer drugs: analytical and
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The author(s) shown below used Federal funds provided by the U.S. Department of Justice and prepared the following final report:
Document Title: Bath Salt-type Aminoketone Designer Drugs: Analytical and Synthetic Studies on Substituted Cathinones
Author(s): Randall Clark, Ph.D.
Document No.: 250125
Date Received: July 2016
Award Number: 2013-DN-BX-K022
This report has not been published by the U.S. Department of Justice. To provide better customer service, NCJRS has made this federally funded grant report available electronically.
Opinions or points of view expressed are those of the author(s) and do not necessarily reflect
the official position or policies of the U.S. Department of Justice.
1
Final Summary Overview, NIJ award 2013-DN-BX-K022
Bath Salt-type Aminoketone Designer Drugs: Analytical and Synthetic Studies on Substituted Cathinones
Purpose of Project:
This project has focused on issues of resolution and discriminatory capabilities in controlled
substance analysis providing data to increase reliability and selectivity for forensic evidence and
analytical data on new analytes of the so-called bath salt-type drugs of abuse. The overall goal of
these studies is to provide an analytical framework for the identification of individual substituted
cathinones to the exclusion of all other possible isomeric and homologous forms of these
compounds. A number of aminoketones or beta-keto/benzylketo compounds (bk-amines) have
appeared on the illicit drug market in recent years including methcathinone, mephedrone,
methylone and MDPV (3,4-methylenedioxypyrovalerone). These substances represent a variety
of aromatic ring substituent, hydrocarbon side chain and amino group modifications of the basic
cathinone/methcathinone molecular skeleton. The broad objective of this research was to
improve the specificity, selectivity and reliability of analytical methods used to identify ring
substituted aminoketones and related compounds. This improvement comes from methods which
allow the forensic analyst to identify specific regioisomeric forms of substituted aminoketones
among many isomers of mass spectral equivalence. Mass spectrometry is the most common
method of confirmation in forensic drug analysis. This project provides methodology and
analytical data to discriminate between those regioisomeric and isobaric molecules having the
same molecular weight and major fragments of equivalent mass (i.e. identical mass spectra).
Furthermore, this work has anticipated the future appearance of some designer aminoketones and
developed reference data and analytical reference standards for these compounds.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
2
Project Subjects:
This project involves basic chemical sciences and focuses on forensic drug chemistry. This
research project did not involve human subjects and no laboratory animals were used in this
work. The project has explored issues of analytical specificity in forensic drug analysis involving
synthetic designer drugs related to cathinone. Cathinone is a natural product found in the leaves
of Catha edulis Forsk, the Khat plant, discovered in Yemen in the eighteenth century.
Cathinone’s stimulatory effects have been known for centuries, mostly prevalent in Middle
Eastern countries ranging from Southern Africa to the Arabian Peninsula. Synthetic cathinones,
the active component in “bath salts,” have surfaced as a popular alternative to other illicit drugs
of abuse, such as cocaine, MDMA (ecstasy), and methamphetamine, due to their potent
psychostimulant and empathogenic effects.
The stimulatory effects of synthetic cathinones are the result of elevations in synaptic
catecholamine concentrations, primarily via two mechanisms. These molecules bind to and
inhibit the monoamine uptake transporters for dopamine, norepinephrine, and serotonin
diminishing their clearance from the synaptic cleft. Second, as substrate releasers, they exhibit
non-exocytotic neurotransmitter release from intracellular stores by reversal of transporter flux
and inhibiting the vesicular monoamine transport receptor. Pyrovalerone and MDPV, the
pyrovalerone–cathinones, represent a subset of cathinone derivatives whose actions occur via
potent and selective monoamine uptake inhibition. MDPV is a potent monoamine transporter
inhibitor with the highest affinity for the dopamine transporter and lowest affinity for the
serotonin transporter. The selectivity of MDPV for the dopamine transporter protein (>100
dopamine/serotonin inhibition ratio) is higher than that described for methamphetamine and
cocaine ratio, >10 and 3.1, respectively, revealing a high abuse potential for this pyrovalerone-
type cathinone derivative.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
3
Project Design:
Based on the structure of the unsubstituted cathinone molecule, designer modifications are
possible in three distinct regions of the molecule: A) the aromatic ring, B) the alkyl side chain;
C) the amino group and a fourth, the carbonyl group (not explored in this project). Based on the
structures of previously identified designer cathinone derivatives, it is clear that designer
modification in regions A, B and C are currently being explored by clandestine chemists.
Futhermore, the strong interest and unique pharmacology of MDPV will likely yield future
designer compounds based on modification of the MDPV molecule. Legal control of a specific
molecule often provides the driving force for clandestine development of additional substituted
cathinone designer molecules. The commercial availability of many sets of precursor substances
further provides additional interest in designer modifications. This project has focused on those
designer concepts used in the amphetamine-type molecules applied to the MDPV series.
Figure 1. Regions for potential designer modifications in the cathinone derivatives.
Figure 2. General structures for the Series I-III bath salt aminoketone derivatives in this study.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
4
Project Methods:
The purpose of this project is to develop regioisomer specific methods for the identification of
ring substituted aminoketone compounds (cathinone derivatives). This work included: 1) the
chemical synthesis of all regioisomeric forms of selected aromatic ring substituted aminoketones,
2) generation of a complete analytical profile for each compound, 3) chromatographic studies to
separate/resolve all regioisomeric aminoketones having overlapping analytical profiles, and 4)
design and validation of confirmation level methods to identify each compound to the exclusion
of other regioisomeric forms.
The initial phase of this work is the organic synthesis of aminoketones of varying aromatic ring
substituents, hydrocarbon side chains and amino groups. In this phase of the work numerous
substituted aminoketones of potential forensic interest have been evaluated. The analytical phases
included chemical characterization, using tools common to forensic science labs such as MS and IR
and these studies were carried out on each of the compounds. The chromatographic retention
properties for each series of isomers have been evaluated by gas and liquid chromatographic
techniques on a variety of stationary phases. These studies have established a structure-retention
relationship for the regioisomers and isobaric aminoketones.
The results of this project will serve to increase the forensic drug chemistry knowledge base for
aminoketone-type designer drugs. When compounds exist which produce the same mass spectrum
(same MW and fragments of equivalent mass) as the drug of interest, the identification by GC-MS
must be based upon the ability of the chromatographic system to resolve these substances. This project
included the synthesis and generation of complete analytical profiles as well as methods of
differentiation for regioisomeric and isobaric substances related to the substituted aminoketones.
This project has generated proactive data for the forensic drug analyst and described a unified
approach for specific drug identification based on structure correlated analytical properties.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
5
Figure 3 illustrates the methods used in our laboratory for the synthesis of the isomers needed to
complete modifications at Regions A, B, and C shown in Figure 1. The starting point in the
synthetic pathway is a substituted benzaldehyde or benzoic acid. Many mono-substituted
benzaldehydes or benzoic acids are available from commercial sources and all six regioisomeric
dimethoxybenzaldehydes are commercially available. The precursor chemicals for all the
possible regioisomeric imposter compounds are commercially available. Isomer issues are not
quite so central in forensic analysis for those natural product drugs (THC, cocaine, etc.)
synthesized by a plant in an enzymatically controlled (isomeric specific) process.
Figure 3. General synthesis for the bath salt aminoketones using the synthesis of MDPV as an example. The analytical methods have focused on those techniques in routine use in forensic laboratories:
GC, GC-MS, IR, GC-IR and related techniques. Additionally some GC-MS/MS product ion
studies have been done as well as some preliminary GC-TOF-MS studies. The initial analytical
studies consisted of a complete profile on each of the amines and ketone, including GC-MS, IR
and GC-IR. The chromatographic elution properties and retention data via capillary GC retention
studies have been collected for each compound followed by the chromatographic evaluation of
each group of compounds based upon structural types. Spectrophotometric techniques such as
infrared spectrophotometry have allowed for the differentiation among some of the aromatic ring
substitution patterns and allow for the detection of those isomeric substances containing a
carbonyl-group in the side chain. With an ample number of structural types available in this
study, the various ring substituents and patterns can be individualized as a result of this work.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
6
Project Data Analysis:
The general approach for the analytical identification of an individual cathinone derivative based
on the results of this work would consist of the generation of a classical electron ionization mass
spectrum (EI-MS). These data should assist with a molecular weight and major fragmentation
between the carbonyl carbon and the alkyl carbon as indicated in Figure 4.
Figure 4. General EI-MS fragmentation for substituted cathinones. The mass of the molecular ion as well as that for the acyl cation (A in Figure 4) helps to identify
the aromatic ring substituents based on mass differentiation from the basic benzoyl fragment
mass. The iminium cation is the base peak in the mass spectrum in our examples studied so far
and this ion provides information on the number of carbons attached to the amine group and the
alkyl side chain in combination. IR and vapor phase GC-IR allow for differentiation of the
aromatic ring substitution patterns. For example GC-IR vapor phase spectra clearly differentiate
the 2,3-methylenedioxy substitution pattern from the 3,4-pattern across a number of side chain
structural categories. Product ion MS-MS studies have provided data on the make-up of the
iminium cation species and allow a clear differentiation of the hydrocarbon content of the tertiary
amine group verses the alkyl side-chain in regioisomeric examples. See the regioisomeric m/z
112 iminium cation structures inside the circle in Figure 4. The synthesis, GC-MS and MS/MS
studies of various deuterium labeled analogues has confirmed these product ion observations.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
7
A series of regioisomeric cyclic tertiary amines were prepared and evaluated in EI-MS and
MS/MS product ion experiments. The cyclic amines azetidine, pyrrolidine, piperidine and
azepane were incorporated into a series of aminoketones related to the cathinone derivative drug
of abuse known as MDPV. Deuterium labeling in both the cyclic amine and alkyl side chain
allowed for the confirmation of the structure for the major product ions formed from the EI-MS
iminium cation base peaks. Each of the regioisomeric m/z 126 base peaks gave a unique and
characteristic major product ion (see Figure 5). An example of the data collected in this work is
presented in the Appendix.
Figure 5. The characteristic product ion MS/MS species from regioisomeric m/z 126 ions.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
8
List of Scholarly Products Produced or in Progress:
The scholarly products for this project will consist of peer reviewed publications in scientific
journals in the field of forensic science, forensic drug chemistry, analytical chemistry and related
subjects. We expect to submit results of this research for publication in national and international
journals such as Journal of Forensic Science, Forensic Science International, Drug Testing and
Analysis, Rapid Communications in Mass Spectrometry, and other appropriate scientific outlets.
We have two manuscripts submitted for publication and under review at this time.
1-Younis F. Hamad Abiedalla, Karim Abdel-Hay, Jack DeRuiter and C. Randall Clark,
“GC-MS and GC-IR Analysis of a Series of Methylenedioxyphenyl-Amino-Ketones:
Precursors, Ring Regioisomers and Side-Chain Homologues of 3,4-Methylene-
dioxypyrovalerone (MDPV),” Drug Testing and Analysis, submitted for publication.
2-Younis F. Hamad Abiedalla, Karim Abdel-Hay, Jack DeRuiter and C. Randall Clark,
“Differentiation of Cyclic Tertiary Amine Cathinone Derivatives by Product Ion Electron
Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, submitted for
publication.
We expect to prepare and submit other manuscripts on additional structural subsets of cathinone
derivatives evaluated in this study. We anticipate the submission of at least two more
manuscripts from this research project.
Implications for Criminal Justice and Practice in the United States:
The appearance of increasing structurally diverse aminoketone derivatives in clandestine samples
highlights several key issues of immediate forensic significance. First, most of these compounds
have regioisomeric analogues which would not be readily differentiated and specifically
identified using standard forensic analytic methodology. The second key issue of forensic
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
9
importance among the aminoketone compounds involves designer drug development. Many of
these compounds contain aromatic substituents known to enhance hallucinogenic or entactogenic
activity in the phenylalkyl-amine (amphetamine and methylenedioxyamphetamine) drugs of
abuse series. As regulatory controls tighten with respect to available aminoketones, designer
derivative exploration and synthesis is expected to continue. This is particularly important in
these aminoketone compounds since the syntheses are relatively straight-forward and many
starting materials are readily accessible. Further designer exploration would likely parallel that
observed in the phenylalkylamine series of drugs and involve methoxy, dimethoxy, bromo-
dimethoxy, methylenedioxy, trifluoromethyl, chloro, and methyl substituents, as well as
regiosiomers of these substitution patterns.
A proactive investigation of the forensic analytical chemistry of these future designer substances
was the objective of this project. The resulting analytical data as well as methods for reference
standard synthesis represent important advancements in forensic drug chemistry. The goal of this
work is to have the data and methods for differentiation among these designer regioisomeric
substances available to assist in drug identification.
The results of this project should provide a detailed framework of analytical properties and
their relationship to drug structure. This project will also provide a scientific framework
for understanding the spectroscopic properties (especially mass spectral fragmentation
chemistry) and chromatographic retention details. These studies will yield synthetic
methods and analytical reference material for rapid production of drug reference
standards. More importantly these results will provide for a more capable scientifically prepared
forensic expert to interact at the interface of the legal system and the science of forensic
drug chemistry.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
10
In July of 2011 the National Drug Intelligence Center (NDIC) issued a “Situation Report”
examining the threat that synthetic cathinone abuse poses to the United States and the
difficulty that U.S. law enforcement faces in preventing the manufacture and distribution of
synthetic cathinones and synthetic cathinone products. The four major concerns in the NDIC
report were as follows: 1-the distribution and abuse of synthetic cathinones in the US will
increase in the near term; 2-more synthetic cathinones will be abused in the long term; 3-
different synthetic cathinones will surface as commercial drug testing companies develop drug
screens to detect existing synthetic cathinones; 4-the global nature of Internet chemical sales,
particularly of synthetic cathinones, will present increasing challenges to U.S. law enforcement
in the long term.
Most of these predictions have now come true and continue to highlight the need to develop
specific, selective and reliable analytical methods to identify existing cathinone products in the
clandestine market place, and versatile methods that can be used to readily identify new designer
analogues as they emerge.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
11
Appendex Material:
This section contains an example of the data generated in this project using one subset of
compounds, the 2,3- and 3,4-methylenedioxyaminoketones. This is a series of homologues and
regioisomers directly related to MDPV.
The EI mass spectra of the isomeric and homologous aminoketones (Compounds 1-6) in
this study are shown below. The base peak in the mass spectra of all these compounds are the
result of the amino-group dominated alpha-cleavage process producing the iminium cation
fragments having homologous and regioisomeric relationships. The base peak in all these
spectra occurs in a mass range of m/z 98, m/z 112 and m/z 126 and represents a homologous
series of iminium cations based on the number of methylenes in the alkyl side-chain. These
iminium cations are the result of fragmentation of the bond between the carbonyl carbon and the
adjacent side chain carbon bearing the amine nitrogen of the pyrrolidine ring. The m/z 149 ion
seen in most of the spectra is the methylenedioxybenzoyl cation (ArCO+) resulting from initial
ionization of the carbonyl oxygen and fragmentation of the same carbon-carbon bond to result in
charge retention on the carbonyl portion of the structure. Loss of CO from the m/z 149 cation is
O
O
O
N O
O
O
N O
O
O
N
O
N
O
N
O
N
OO
OO
OO
(1) (2) (3)
(4) (5) (6)
MDPV
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
12
the likely source of the m/z 121 cation observed in most of the spectra. The iminium cation
essentially characterizes the nature of the alkylamino-group attached to the carbonyl carbon,
however these ions as well as the substituted benzoyl cations and resulting fragments do not
provide characterization of the regioisomeric position of the methylenedioxy-group.
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Scan 755 (7.487 min): 141110-121.D\data.ms98.2
56.1
149.1121.177.1 245.1215.1175.1 195.1 293.0273.0
N
OOO
(1)
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Average of 7.499 to 7.622 min.: 141110-119.D\data.ms112.2
65.141.1 149.191.1 215.0 237.0 293.0259.1131.1 172.1 197.0
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
13
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Scan 804 (7.773 min): 141110-120.D\data.ms126.2
65.142.1 149.196.1 215.0 237.0 293.0273.1177.1 197.0 255.0
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Scan 782 (7.645 min): 141118-09.D\data.ms98.1
56.1
121.1 149.177.1 215.0177.1 237.0 293.0272.9
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
14
EI mass spectra of the six regioisomeric and homologous methylenedioxy aminoketones.
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Scan 807 (7.791 min): 141118-09.D\data.ms112.2
65.141.1 149.191.1 232.1177.1131.1 204.1 261.1 293.0
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Abundance
Average of 7.977 to 8.070 min.: 141118-09.D\data.ms126.2
65.1149.142.1 96.1
232.2177.1 204.2 273.1 293.0
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
15
Capillary gas chromatographic separation of the six regioisomeric and homologous methylenedioxy aminoketones using Rtx-5 stationary phase.
The chromatogram above shows the GC separation of the six regioisomeric and
homologous methylenedioxyphenylaminoketones in this study. The separation was obtained on a
30 meter capillary column coated with Rtx-5, 5% diphenyl and 95% dimethylpolysiloxane. The
elution order reflects these structure-chromatographic relationships showing increased retention
with increasing side chain length for the homologous series. Compounds 1 and 4 show the lowest
retention and both represent the methyl side chain, this is followed by the ethyl side chain for
compounds 2 and 5, and the highest retention occurs for the n-propyl side chain for compounds 3
and 6. Furthermore, within each pair of equivalent homologues the position of the ring
methylenedioxy substitution controls the relative retention of the pair. In every case the 2,3-
isomer elutes before the 3,4-isomer, for example MDPV (the 3,4-methylenedioxyphenyl isomer,
compound 6) has much higher retention (about 4 minutes) than its’ corresponding 2,3-isomer,
compound 3.
6 3
5
2
4
1
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TIC: 141125-89.D\data.ms
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
16
The vapor phase infrared spectra generated in GC-IR experiments are shown below.
These spectra were generated directly from the chromatography peak as each compound eluted
from the capillary GC column. Thus these infrared spectra have an added level of reliability
based on the purity of the gas chromatographic peak. The GC-IR vapor phase infrared spectra
were recorded in the range of 4000 – 550 cm-1 with a resolution of 8 cm-1. All these compounds
show a carbonyl band in the 1690 cm-1 range and characteristic bands in the 1500 cm-1 to 1200
cm-1 range. The characteristic bands in the 1500 cm-1 to 1200 cm-1 range provide information
concerning the position of the methylenedioxy ring and its relationship to the aminoketone side
chain. The 2,3-methylenedioxy substitution pattern in compounds 1, 2 and 3 show a
characteristic pattern in the 1500 cm-1 to 1200 cm-1 range consisting of a strong single band
absorption centered in the 1447 cm-1 range and a less intense doublet peak in the 1254/1220 cm-1
range. However, the 3,4-methylenedioxy substitution pattern in compounds 4, 5 and 6 show a
doublet pattern with peaks centered at 1485 cm-1 and 1436 cm-1 in all three spectra and an
intense singlet absorption band at 1446 cm-1.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
17
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This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
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This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
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This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
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This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
21
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1450
1401
1358
1241
1117
1065
952
876
835
771
729
640
OOO
100020003000Wavenumbers
50
60
70
80
90
100
Perc
ent T
rans
mit
tanc
e
3082
3015
2965 2940
2883
2778 18
39
1696
1613
1486
1439
1347
1249
1089
1049
945
887
806
768
722
657
622
572
O
O
O
50010001500200025003000Wavenumbers
40
60
80
100
Per
cent
Tra
nsm
itta
nce
3079
3016
2955
2922
2890
2836 2
807
2727
1713
1635 1
605
1539
1504
1461
1389
1231
1175
1117
1065
991
934
840
772
725
695
H
OOO
100020003000Wavenumbers
40
50
60
70
80
90
100
Perc
ent
Tra
nsm
itta
nce
3022
2913
2889
2816
2773
2718
1715
1611
1488
1446
1393
1347
1252
1091
1048
938
876
806
788
622
586
O
O
O
H
100020003000Wavenumbers
85
90
95
100
Per
cent
Tra
nsm
ittan
ce
3081
2969
2882
2817
1767
1697
1652
1630 15
9415
5715
4015
0714
4613
9613
5812
5412
2011
5010
6795
089
584
2 772
733
OOO N
2,3-MDPV
100020003000Wavenumbers
85
90
95
100
Per
cent
Tra
nsm
ittan
ce
3081
2967
2882
2812
1750
1731
1689
1654
1613
1555
1538
1485 14
3613
4312
46
1094
1049
945
895
868
806 57
4
O
O
O
N
3,4-MDPV
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
22
100020003000Wavenumbers
85
90
95
100
Perc
ent T
rans
mit
tanc
e
3081
2967
2882
2812
1750
1731
1689
1654
1613
1555
1538
1485 14
3613
4312
46
1094
1049
945
895
868
806 57
4
O
O
O
N
(6)
3,4-MDPV
100020003000Wavenumbers
85
90
95
100
Per
cent
Tra
nsm
ittan
ce
3081
2969
2882
2817
1767
1697
1652
1630 15
9415
5715
4015
0714
4613
9613
5812
5412
2011
5010
67
950
895
842 77
273
3
O
N
OO
(3)2,3-MDPV
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
23
The cyclic amines azetidine, pyrrolidine, piperidine and azepane were incorporated into a series
of aminoketones related to the cathinone derivative drug of abuse known as MDPV. Deuterium
labeling in both the cyclic amine and alkyl side chain allowed for the confirmation of the
structure for the major product ions formed from the EI-MS iminium cation base peaks. These
iminium cation base peaks show characteristic product ion spectra which allow differentiation of
the ring and side chain portions of the structure. The small alkyl side chains favor ring
fragmentation in the formation of the major product ions. The higher side chain homologues
appear to promote product ion formation by side chain fragmentation. Both side chain and ring
fragmentation yield a mixture of product ions in the piperidine and azepane series.
The following mass spectra and product ion spectra show the results for the regioisomeric cyclic
tertiary amines related to MDPV.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
24
40 60 80 100 120 140 160 180 200 220 240 2600
500000
1000000
1500000
2000000
2500000
3000000
3500000
m/z-->
Abundance
Scan 901 (8.338 min): 150505-49.D\data.ms126.2
42.1 149.165.1244.196.1 273.1216.1166.1 190.1
40 60 80 100 120 140 160 180 200 220 240 2600
200000
400000
600000
800000
1000000
1200000
1400000
1600000
1800000
m/z-->
Abundance
Scan 848 (8.029 min): 141118-09.D\data.ms126.2
65.1149.142.1 96.1
232.1177.1 215.1 274.1197.0 257.1
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
25
EI-MS for the four regioisomeric cathinone derivatives of MW= 275 and regioisomeric base peak iminium cations at m/z 126.
40 60 80 100 120 140 160 180 200 220 240 2600
200000
400000
600000
800000
1000000
1200000
1400000
1600000
1800000
m/z-->
Abundance
Average of 8.298 to 8.379 min.: 150427-68.D\data.ms126.2
41.1 65.1 149.184.1 166.1 273.1246.2190.1105.1 218.1
m/z 126
N
40 60 80 100 120 140 160 180 200 220 240 2600
100000
200000
300000
400000
500000
600000
700000
800000
900000
1000000
1100000
1200000
1300000
m/z-->
Abundance
Scan 950 (8.624 min): 150529-64.D\data.ms126.2
55.1 165.0
91.172.1273.1244.1147.1108.1 203.0186.0
O
O
N
O
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
26
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
27
MS/MS product ion spectra for the four regioisomeric m/z 126 base peak iminium cations.
This document is a research report submitted to the U.S. Department of Justice. This report has not been published by the Department. Opinions or points of view expressed are those of the author(s)
and do not necessarily reflect the official position or policies of the U.S. Department of Justice.
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