Bath Salt-Type Aminoketone Designer Drugs: Analytical and Synthetic Studies on Substituted Cathinones

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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. 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. 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.

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.

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.

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.

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.

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.

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

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.

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 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.

O O O O O O O N O N O N

(1) (2) (3)

O O O

O N O N O N

O O O (4) (5) (6)

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

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.

Abundance

Scan 755 (7.487 min): 141110-121.D\ data.ms 98.2 4000000 O O 3500000 O N 3000000

2500000 (1)

2000000

1500000

1000000

56.1 500000 149.1 77.1 121.1 175.1 195.1 215.1 245.1 273.0 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z-->

Abundance

Average of 7.499 to 7.622 min.: 141110-119.D\ data.ms 220000 112.2

200000

180000

160000

140000

120000

100000 80000 60000

40000

20000 65.1 41.1 149.1 91.1 131.1 172.1 197.0 215.0 237.0 259.1 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m /z-->

Abundance

Scan 804 (7.773 min): 141110-120.D\ data.ms 126.2 1600000

1400000

1200000

1000000

800000

600000

400000

200000 65.1 42.1 96.1 149.1 177.1 197.0 215.0 237.0 255.0 273.1 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z-->

Abundance

Scan 782 (7.645 min): 141118-09.D\ data.ms 1200000 98.1 1100000 1000000

900000

800000

700000

600000

500000

400000 300000 200000 56.1

100000 121.1 149.1 77.1 177.1 215.0 237.0 272.9 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z-->

Abundance

Scan 807 (7.791 min): 141118-09.D\ data.ms 112.2 1800000

1600000

1400000

1200000 1000000 800000

600000

400000

200000 65.1 41.1 149.1 91.1 131.1 177.1 204.1 232.1 261.1 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z-->

Abundance Average of 7.977 to 8.070 min.: 141118-09.D\data.ms 126.2 600000 550000 500000

450000

400000

350000

300000

250000

200000 150000 100000

50000 65.1 42.1 96.1 149.1 177.1 204.2 232.2 273.1 293.0 0 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z-->

EI mass spectra of the six regioisomeric and homologous methylenedioxy aminoketones.

TIC: 141125-89.D\ data.ms

55000 1 50000

45000

40000 5

35000 4 3 6 30000

25000 2 20000

15000

10000

40.00 42.00 44.00 46.00 48.00 50.00 52.00 54.00 56.00 58.00 60.00 62.00 64.00 66.00 68.00 Time--> 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.

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.

788 1766 835 3081 1594 1557 1540 1652 1631 1507 1396 752 736 95 896 1361 2813

2882 O O 1068 90 O N 945 2971 1700 1255

Percent Transmittance Percent (1)

85 1223 1447

3000 2000 1000 Wavenumbers

100

1557 1539 1593 3081 1504 894 1630 774 1396 732 842 1150 90 1358 2816

950 O O

O 1067 2882 N 1697

80 1254

Percent Transmittance Percent (2) 2969 1220

70 1446

3000 2000 1000 Wavenumbers

1767 1557 1594 1540 3081 895 1652 1507 1630 772 1396 733 95 842 1150 1358

2817

O O 950 O N 1067 90 2882 1697 1254 (3) Percent Transmittance Percent 2,3-MDPV 2969

85 1220

1446

3000 2000 1000 Wavenumbers

575 3081 770 1556 1538 1652 811

95 877 1613 1105 2815 945 1344 2885 2947 90 O 1049 1692 2973 O N 1436 1485 85 O (4) Percent Transmittance Percent

1246 75

3000 2500 2000 1500 1000 500 Wavenumbers

100

886 919 803 944 1612

90 2810 1095 1345 2884

O 1689 1049 O N 1436 2970 80 1485 O

Percent Transmittance Percent (5)

70 1245

3000 2000 1000 Wavenumbers

100

574 1750 3081 1731 895 1555 868 1538 1654 806 945 1613 2812

1094

95 1343 O 2882 1689 1049 O N 1436

O 1485 2967 (6) 90

Percent Transmittance Percent 3,4-MDPV

85 1246

3000 2000 1000 Wavenumbers

876 586 622 3022 991 1539 695 3079 90 3016 1605 1117 1504 840 2773 2889 2718 2913 1393 2816 2727 788 806

2955 2807 1635 1611 938 725 1091 2922 1347 80 2890 2836 1389 1175 80

934 1048 772 1488 70 60 O O 1065 O 1446

Percent Transmittance O Percent Transmittance Percent O

H 60 H 1715 O 40 50 1713 1461 1231 1252

40 3000 2500 2000 1500 1000 500 3000 2000 1000 Wavenumbers Wavenumbers

100 100

657 622 1839 722 640 768 1555 1538 572 3082 2778 90 876 887 2778 1594

90 3015 835 3081 3012 1631 806 1117 1401 945 1613 771 729 1089 1358

80 2883 80 1347 2940 2965 2881 1049 70 952 2963 2942 1696 1486

1065 70 1439 O 1700 1241 Percent Transmittance Percent Percent Transmittance Percent 60 O O O 60 O

50 O 50 1450 1249 40 3000 2500 2000 1500 1000 500 3000 2000 1000 Wavenumbers Wavenumbers

100 100

574 1750 1767 3081 1731 895 1555 868 1557 1538 1594 1540 1654 3081 895 806 1652 1507 1630 772 1396 945 1613 733 842

95 2812

1150 1358 1094 1343 2817 95 2882

950 1689 1049 1067 1436 2882

90 1485 2967 1697 1254 90 Percent Transmittance Percent O O Transmittance Percent O 2969 O N O N 85 1220 O 1446 1246 2,3-MDPV 85 3,4-MDPV

3000 2000 1000 3000 2000 1000 Wavenumbers Wavenumbers 21

100

1767 1557 1594 1540 3081 895 1652 1507 1630 772 1396 733 95 842 1150 1358 2817

O O 950 O N 1067 90 2882 1697 1254 (3) Percent Transmittance Percent 2,3-MDPV 2969

85 1220

1446

3000 2000 1000 Wavenumbers

100

574 1750 3081 1731 895 1555 868 1538 1654 806 945 1613 2812

1094

95 1343 O 2882 1689 1049 O N 1436

O 1485 2967 (6) 90

Percent Transmittance Percent 3,4-MDPV

1246 85

3000 2000 1000 Wavenumbers

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.

Abundance

Scan 901 (8.338 min): 150505-49.D\ data.ms 126.2 3500000

3000000

2500000

2000000

1500000

1000000

500000 42.1 65.1 149.1 96.1 244.1 166.1 190.1 216.1 273.1 0 40 60 80 100 120 140 160 180 200 220 240 260 m /z-->

Abundance

Scan 848 (8.029 min): 141118-09.D\ data.ms 126.2 1800000

1600000

1400000

1200000

1000000 800000

600000

400000

200000 65.1 42.1 96.1 149.1 177.1 197.0 215.1 232.1 257.1 274.1 0 40 60 80 100 120 140 160 180 200 220 240 260 m /z-->

Abundance

Average of 8.298 to 8.379 min.: 150427-68.D\ data.ms 126.2 1800000

1600000

1400000

1200000

1000000

800000

600000

400000

200000 41.1 65.1 149.1 84.1 105.1 166.1 190.1 218.1 246.2 273.1 0 40 60 80 100 120 140 160 180 200 220 240 260 m /z-->

Abundance

Scan 950 (8.624 min): 150529-64.D\ data.ms 1300000 126.2 1200000 1100000 1000000 900000 800000 O N N 700000 O

600000 m/z 126 O 500000

400000

300000

200000

55.1 165.0 100000 72.1 91.1 108.1 147.1 186.0 203.0 244.1 273.1 0 40 60 80 100 120 140 160 180 200 220 240 260 m /z-->

EI-MS for the four regioisomeric cathinone derivatives of MW= 275 and regioisomeric base peak iminium cations at m/z 126.

MS/MS product ion spectra for the four regioisomeric m/z 126 base peak iminium cations.