Forensic Science International 217 (2012) 139–145

The characterisation of two halogenated cathinone analogues:3,5-Difluoromethcathinone and 3,5-dichloromethcathinone

Sean Davis a,*, Karen Rands-Trevor a, Sue Boyd b, Methsiri Edirisinghe a

a Queensland Health Forensic and Scientific Services (QHFSS), 39 Kessels Rd, Brisbane, Australiab School of Biomolecular and Physical Sciences, Griffith University, Brisbane, Australia

A R T I C L E I N F O

Article history:

Received 28 July 2011

Received in revised form 17 October 2011

Accepted 19 October 2011

Available online 15 November 2011

Keywords:

3,5-Difluoromethcathinone

3,5-Dichloromethcathinone

3,5-Difluoro-isomethcathinone

Designer drug

Mass spectra

IR

A B S T R A C T

Australia has seen an increase in the importation and use of drugs that are marketed and sold as ‘‘Legal

Highs’’. These compounds have largely tended to be various cathinone analogues, with 4-

methylmethcathinone the most prominent to date. In January 2009, unknown samples were submitted

for analysis along with a large seizure of 3-fluoromethcathinone as part of a police operation. The samples

were analysed and determined to be 3,5-difluoromethcathinone and 3,5-dichloromethcathinone. These

compounds were synthesised and characterised. The GC–MS data of the samples and their N-acetyl

derivatives, NMR, vapour-phase and condensed-phase IR for these previously unreported compounds are

presented. This analytical data will enable laboratories to confirm the presence of these compounds in

the absence of commercially available reference standards.

� 2011 Elsevier Ireland Ltd. All rights reserved.

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jou r nal h o mep age: w ww.els evier . co m/lo c ate / fo r sc i in t

1. Introduction

The designer drug market has recently seen an increase in thenumber of drugs sold as ‘legal highs’. One prominent group ofcompounds consist of analogues of cathinone, namely 4-methyl-methcathinone (mephedrone) 1, 3-fluoromethcathinone 2, and 3,4-methylenedioxy-methcathinone (methylone) 3. Compounds 1, 2and 3 are based on the secondary amine methcathinone, which hasbeen found to be more potent than the naturally occurring primaryamine cathinone 4 [1]. These analogues are marketed and sold in avariety of countries including Australia and the UK as ‘‘dietarysupplements’’, ‘‘herbal highs’’ and ‘‘party pills’’ in an apparentattempt to thwart controlled drug legislation [2]. In Australia, thishas resulted in an increased prevalence of these compounds,particularly in the use and availability of mephedrone [3].

The principle purpose for the manufacturers of these analoguesis to attempt to circumvent existing controlled substancelegislation. However, the primary driving force for the consumersof ‘‘legal highs’’ such as mephedrone is its availability, with legalitya secondary motive [4]. The increasing popularity of mephedronecan arguably be attributed to: (1) the convenience of on-linepurchasing; and (2) a reduction in the quality and availability ofecstasy. This popularity amongst users has also been assisted bymephedrone reportedly having similar psychoactive effects as

* Corresponding author. Tel.: +61 7 32749038.

E-mail address: sean_davis@health.qld.gov.au (S. Davis).

0379-0738/$ – see front matter � 2011 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.forsciint.2011.10.042

ecstasy [5]. The legislation of mephedrone did not immediatelyresult in a significant decline in its availability as a ‘‘Legal High’’ inthe UK. After mephedrone became scheduled in the UK in April2010, ‘legal highs’ purchased after this date were still found tocontain this compound and other controlled substances [6].

As these ‘legal highs’ become legislated and availabilitydecreases over time, new compounds are expected to be producedby altering the chemical structure of existing drugs of abuse. It istherefore not viable or practical to specifically legislate against allvariants when they appear. This means that without adequateanalogue and derivative clauses manufacturers and consumerswill continue to exploit legislative gaps to create ‘‘legal highs’’. Thiswill also result in an increased number of analogues of existingillicit drugs, such as those based on the cathinone structure. Thiscan already be seen with the increasing number of structurallyrelated a-pyrrolidinophenones, which are seen in countries suchas Germany. This provides further evidence of the developingnature of the designer drug market [7].

In January 2009, as part of a police operation, what wasdetermined to be compound 2 and two unknown samples weresubmitted for analysis in Queensland, Australia. The unknownsamples were contained in clip sealed plastic bags which werelabelled ‘‘1-(3,5-di chlorophenyl)-2-(methylamino) propanone’’and ‘‘1-(3,5-difluorophenyl)-2-(methylamino) propanone’’. Thesepowders were analysed and determined to contain 3,5-difluor-omethcathinone 5, and 3,5-dichloromethcathinone 6 (Fig. 1).While these two compounds are not specifically listed in controlleddrug legislation in Queensland, the provision of analogue and

Fig. 1. Analogues of cathinone: 4-methylmethcathinone 1 3-fluoromethcathinone 2 3,4-methylenedioxymethcathinone 3 cathinone 4 3,5-difluoromethcathinone 5 3,5-

dichloromethcathinone 6 and bupropion 7.

S. Davis et al. / Forensic Science International 217 (2012) 139–145140

derivative clauses in the legislation would classify these com-pounds as dangerous drugs in this jurisdiction [8].

It is vital that a forensic laboratory be able to positively identifythese compounds for the benefit of law enforcement, the judiciary andthe community at large. The absence of reference standards andreferencelibraryspectrameansthataforensicchemistmaynotbeableto identify these substances through routine analytical protocols. As isoften seen with new designer drugs on the market, while referencestandards may eventually becomeavailablethis usually does notmeetthe time constraints prevalent in a busy forensic laboratory.

While a number of mono-substituted fluorinated cathinonesand amphetamines have already been encountered on the market,so far there has not been the same observed number of chlorinatedcompounds. One compound that is readily available and analogousto cathinone is the anti-depressant bupropion 7 [9]. Severaldifferent analogues of bupropion have been synthesised andexamined as indirect dopamine agonists for cocaine addiction [10].

3,5-Difluoromethcathinone and 3,5-dichloromethcathinonehave not previously been reported in the literature. Thereforethis laboratory has undertaken the syntheses of referencematerials to compare against the samples (Schemes 1 and 2).The synthesis and characterisation of these compounds will enablethe forensic chemist to meet the analytical challenges successfully.The analytical profiles are presented.

2. Materials and methods

2.1. GC–MS

A small quantity of each powder was extracted in methanol and 0.2 mL of each

extract was injected into the GCMS.

Scheme 1. Formation of 3,5-difluoromethcathinone hydrochlori

Scheme 2. Formation of 3,5-dichloromethcathinone hydrochloride. a. EtMgBr, TH

Derivatisation was achieved by adding an excess of acetic anhydride to a methanol

solution of the sample. The liquid was then agitated for several minutes to allow the

reaction to reach completion, before being injected (0.2 mL) into the GCMS.

Electron Impact (EI) mass spectra were obtained using an Agilent 6890N gas

chromatograph fitted with a 5975 inert mass selective detector. The column was a

HP-5 capillary column (30 m � 0.25 mm � 0.25 mm) with helium as the carrier gas

at a constant flow of 0.9 mL min�1 and a split ratio of 25:1. The injector was heated

to 280 8C and the temperature program was 100 8C for 1 min, ramped at 30 8C/min

until reaching a temperature of 280 8C at which the temperature remained for

10 min. The mass spectra were collected after a 2.5 min solvent delay using a 40–

450 m/z scan range at 3.51 scans s�1.

2.2. Vapour phase infrared analysis

The samples were prepared as described in Section 2.1, with an injection volume

of 4 mL.

The vapour phase infrared spectra were collected using an Agilent 7890 gas

chromatograph equipped with an ASAP IRD II infrared detector. The carrier gas was

helium at a constant flow of 4.1 mL min�1; the column was HP-5 capillary column

(30 m � 0.32 mm � 0.25 mm). The injector was set at a pulsed split of 24 psi for

2 min with a split ratio of 1:1 and a temperature of 280 8C. The temperature

program was 100 8C for 2 min, ramped at 20 8C/min until reaching a temperature of

280 8C at which the temperature remained for 8 min. The temperature of the light

pipe and the flow cell in the detector were both 280 8C. The spectra were obtained

from 4000 to 550 cm�1.

2.3. Condensed phase infrared analysis

The Fourier Transform Infrared Analysis was collected using a Thermo Nicolet

5700 FTIR with a Smart Orbit Diamond Attenuated Total Reflectance (ATR)

attachment. The infrared spectrum was obtained from 4000 to 400 cm�1.

2.4. NMR analysis

Samples were run in d6-DMSO. Spectra were acquired on a Varian 400 MHz Unity

INOVA spectrometer operating at 400 MHz (1H) and 100 MHz (13C).

de. a. Br2, CH2Cl2, RT, 30 min, 95%; b. CH3NH2, RT, 2 h, 27%.

F, RT, 18 h, 64%; b. Br2, CH2Cl2, RT, 18 h, 45%; c. CH3NH2, THF, RT, 1 h, 17%.

S. Davis et al. / Forensic Science International 217 (2012) 139–145 141

2.5. Reagents

All reagents were purchased from commercial sources and were used without

further purification.

3. Synthesis

3.1. 3,5-Difluoromethcathinone hydrochloride (Scheme 1) [11]

3.1.1. 1-(3,5-Difluorophenyl)-2-bromopropanone

A solution of Br2 in CH2Cl2 (1 M, 9.59 g, 60 mmol) was addeddropwise to a stirred solution of 3,5-difluoropropiophenone inCH2Cl2 (10 g, 59 mmol, 50 mL). Upon completion of the addition,the solvent and excess Br2 were removed under vacuum. Theresidue was diluted with CH2Cl2 and washed with sat. aq. sodiumthiosulphate solution (3�) to afford 1-(3,5-difluorophenyl)-2-bromopropanone (14 g, 95%) as a light yellow oil, which was usedin subsequent chemical steps without further purification.

3.1.2. 3,5-Difluoromethcathinone hydrochloride

A solution of CH3NH2 in THF (2 M, 0.8 mL, 1.6 mmol) was addeddropwise to a stirred solution of 1-(3,5-difluorophenyl)-2-bromo-propanone (200 mg, 0.8 mmol) in THF (1.4 mL) and the resultantmixture stirred at room temperature for 2 h. After removal of excessCH3NH2 in vacuo, the remaining residue was diluted with 1 M HCland washed with Et2O. The aqueous layer was adjusted to pH 12with 20% aq. NaOH, extracted (Et2O 3�), dried (Na2SO4) and solventremoved in vacuo to afford 3,5-difluoromethcathinone as a yellowoil. The free base was diluted with Et2O and treated with anhydrousHCl gas giving 3,5-difluoromethcathinone hydrochloride (50 mg,27%) as a white solid, which was visually pure by GCMS.

3.2. 3,5-Dichloromethcathinone hydrochloride (Scheme 2) [12]

3.2.1. 3,5-Dichloropropiophenone

Ethyl magnesium bromide in Et2O (3 M, 4.7 mL, 1.4 mmol) wasadded to a stirred solution of 3,5-dichlorobenzonitrile (1 g,5.8 mmol, 0 8C) in anhydrous THF (21 mL) and the reactionmixture left to stir at room temperature for 18 h. The mixturewas then cooled (0 8C) and the reaction quenched with HCl (0.1 M).After stirring for 1 h at room temperature, the mixture was basifiedwith water and NH4OH. The aqueous layer was extracted (CH2Cl2

3�) and the combined organic layers were dried (Na2SO4) and

Fig. 2. Electron impact mass spectrum for (a) 3,5-difluoromethcathinone (b) suspected 3

acetyl-3,5-difluoromethcathinone.

filtered. Solvent removal in vacuo gave 3,5-dichloropropiophenoneas a crude yellow oil. The crude oil was subjected to columnchromatography (SiO2, 5% EtOAc/hexanes) to furnish 3,5-dichlor-opropiophenone (760 mg, 64%) as a clear oil.

3.2.2. 1-(3,5-Dichlorophenyl)-2-bromopropanone

Br2 (882 mg, 5.5 mmol) was added dropwise to a solution of3,5-dichloropropiophenone (590 mg, 2.9 mmol) in CH2Cl2 (20 mL).Initially a small quantity of Br2 was added to initiate the reaction.The remaining Br2 was then added slowly. After stirring at roomtemperature for 18 h, the excess Br2 was removed in vacuo. Theresidue was then diluted with CH2Cl2 and washed with sat. aq.NaHCO3 and sat. aq. sodium thiosulphate (3�). The organic layerwas dried (Na2SO4) and filtered. Solvent removal in vacuo gavecrude 1-(3,5-dichlorophenyl)-2-bromopropanone as an orange oil.The crude oil was subjected to column chromatography (SiO2, 16%CH2Cl2/hexanes) to furnish 1-(3,5-dichlorophenyl)-2-bromopro-panone (370 mg, 45%) as a clear oil.

3.2.3. 3,5-Dichloromethcathinone hydrochloride

A solution of CH3NH2 in THF (2 M, 0.890 mL, 1.8 mmol) wasadded dropwise to a stirred solution of 1-(3,5-dichlorophenyl)-2-bromopropanone (250 mg, 0.9 mmol) in THF (1.5 mL). The resultantmixture was stirred at room temperature for 1 h. After removal ofexcess CH3NH2 in vacuo, the remaining residue was diluted with 10%aq. HCL and washed with Et2O. The aqueous layer was adjusted to pH12 with 20% aq. NaOH and extracted (Et2O 3�), dried (Na2SO4), andsolvent removed in vacuo to provide 3,5-dichloromethcathinone(130 mg, 62%) as a yellow oil. The free base was diluted with Et2Oand treated with anhydrous HCl gas giving 3,5-dichloromethcathi-none hydrochloride (40 mg, 17%) as an off-white solid, which wasvisually pure by GCMS.

4. Results and discussions

4.1. Mass spectrometry

4.1.1. 3,5-Difluoromethcathinone

Fig. 2 shows the comparison between the EI mass spectrum of3,5-difluoromethcathinone synthesised ‘in-house’ and the samplecontaining the suspected 3,5-difluoromethcathinone and theircorresponding N-acetyl derivatives. Both spectra (Fig. 2) contain

,5-difluoromethcathinone (c) N-acetyl-3,5-difluoromethcathinone (d) suspected N-

Fig. 3. Major EIMS fragmentations for 5 and 6.

S. Davis et al. / Forensic Science International 217 (2012) 139–145142

the molecular ion (M+) m/z 198 in the mass spectrum with a smallintensity that is consistent with the mono-substituted fluorinatedmethcathinone [11]. The base peak at m/z 58 is due to theimmonium ion formed from the amine initiated a-cleavage, whichis a characteristic ion for the class of N-methyl phenethylaminessuch as methcathinone. Significant fragments are also observed atm/z 141 and m/z 113, which correspond to the difluorobenzyloxycation and difluorophenyl cation, respectively [13] (Fig. 3). A minorion at m/z 184 is due to the loss of the a-methyl through the amine-initiated alpha-cleavage [14].

N-acetyl-3,5-difluoromethcathinone has a monoisotopic massof 241 due to the addition of an acetamide moiety onto thesecondary amine. The subsequent a-cleavage of the amide givesthe acetyl imine species with an ion at m/z 100 [15]. This isconsistent with the acetyl derivatives of N-methyl phenethylaminecompounds [16]. The MacLaferty rearrangement has beenobserved previously to produce a prominent cation with regioi-somers of fluoroamphetamine [17]. As with the mono-substitutedisomers of fluoromethcathinone the presence of the a-carbonyl onthe molecule inhibited this rearrangement [11]. The mass spectraof the synthesised 3,5-difluoromethcathinone and the correspond-ing acetyl derivative agreed with those of the submitted sample(Fig. 2).

It was observed that there was a prominent impurity in the GCchromatogram of the suspected sample of 3,5-difluoromethcathio-none. The unknown peak had a ratio of 2:1 of by-product to 3,5-difluoromethcathionone. It was suspected that this larger peak was aby-product that preferentially formed during the production process.While optimising the conditions for the synthesis of 3,5-difluor-omethcathionone, it was found that allowing the reaction to proceedovernight at room temperature resulted in the formation of theundesired by-product, which had a significant impact on the yield.

3-Fluoro-isomethcathinone 8 (Fig. 4) has been identified as aby-product in the synthesis of 3-fluoromethcathinone [18]. The 3-fluoro-isomethcathinone has a base peak of m/z 138 arising fromthe monofluorophenylimmonium cation. The mass spectra of iso-

Fig. 4. 3-Fluoro-isomethcathinone 8 iso-mephedrone 9 iso-e

mephedrone 9 and iso-ethcathinone 10 have previously beenreported in the literature as by-products in samples of mephe-drone and ethcathinone by McDermott et al. [19]. The twocompounds both have a base peak of m/z 134, which is consistentwith the equivalent fragmentation pattern of compound 8.McDermott et al. proposed that the formation of the isomericby-products 9 and 10 was most likely due to a rearrangementthrough the formation of a a-hydroxyimine intermediate [19].

The undesired by-product can be seen in the mass spectra(Fig. 5) to have a weak molecular ion (M+) of 198 and a base peak ofm/z 156, which corresponds with the expected difluoropheny-limmonium ion. This compound is, therefore, tentatively identifiedas 3,5-difluoro-isomethcathinone 11. It is likely that the submittedsample, which also contained the characteristic by-product, wassubjected to reaction conditions similar to those used ‘in-house’. Ithas been proposed that the presence of the isomeric by-productsindicated that liquid methylamine had been used to synthesise thetarget compounds [19]. In contrast to the formation of compounds9 and 10 using liquid methylamine, we found that the use ofmethylamine in THF also formed the isomeric impurity 11. Thissuggests that the presence of an isomeric impurity is not aneffective indication of the form of methylamine used in thereaction. The N-acetyl derivative of compound 11 is provided inFig. 5, with an observed increased intensity of the m/z 198 ion,which forms from the cleavage of the acetyl group. The presence of11 in both the submitted and synthesised samples adds furthersupport to the identity of 3,5-difluoromethcathionone. Furtherinvestigation is required to confirm the identity of compound 11.

4.1.2. 3,5-Dichloromethcathinone

Fig. 6 shows a comparison between the EI mass spectrum for3,5-dichloromethcathinone, the unknown sample and theircorresponding N-acetyl derivatives. 3,5-Dichloromethcathinonegives a weak molecular ion (M+) of 230 and an expected base peakof m/z 58. The 3,5-dichloromethcathinone compound provides thecations m/z 173 and m/z 145 (Fig. 3). Further, the m/z 145 has theobserved characteristic isotope pattern (9:6:1) consistent withdichlorinated compounds. N-acetyl-3,5-dichloromethcathinonehas a molecular ion (M+) of 273 with the expected m/z 100cation. The correlation between the spectra (Fig. 6) adds furtherweight to the identity of the submitted sample as 3,5-dichlor-omethcathinone.

4.2. NMR spectroscopy

O

NH HCl

13'

2'

2

3

4'

5'

6'

1'

X

X

X = FCl

Me

thcathinone 10 and 3,5-difluoro-isomethcathinone 11.

Fig. 5. EIMS for (a) compound tentatively identified as 3,5-difluoro-isomethcathinone (b) sample containing compound tentatively identified as 3,5-difluoro-

isomethcathinone and the N-acetyl derivatives (c) and (d), respectively.

S. Davis et al. / Forensic Science International 217 (2012) 139–145 143

As 3,5-difluoromethcathinone 5 was a minor componentcompared to the suspected undesired structural isomer 11 inthe sample submitted to the laboratory, the NMR was conductedon the compound synthesised ‘in-house’. While the submittedsample of 3,5-dichloromethcathinone 6 was sufficiently clean itwas found that both 5 and 6 were unstable in protic solvents. Thisresulted in the observation of extensive degradation products inattempts to analyse the free bases using 1H and 13C NMRspectroscopy. The methcathinone derivatives were thereforeanalysed as their respective hydrochloride salts.

4.2.1. 3,5-Difluoromethcathinone.HCl

In the observed 1H and 13C NMR spectra the chemical shiftswere closely related to those observed for the mono-fluorinatedanalogue 2 [11]. The presence of fluorine in a molecule can result insplitting of the peaks in the aromatic region due to spin–spincoupling with both the 1H and 13C NMR. The 13C spectrum of thecompound was complicated by the second order multiplicityobserved in the 13C resonances in the aromatic region of thespectrum, due to the magnetic inequivalence of the two chemicallyequivalent 19F substituents.

Fig. 6. EIMS for (a) 3,5-dichloromethcathinone (b) suspected 3,5-dichloromethcath

dichloromethcathinone.

1H (400 MHz, d6-DMSO, 298 K): d 7.77 (2H, m, H20,60), 7.71 (1H,tt, J = 8.4, 2.3 Hz, H40), 5.21 (1H, q, J = 7.2 Hz, H2), 2.58 (3H, s, N-Me), 1.43 (3H, d, J = 7.2 Hz, H3).

13C (100 MHz, d6-DMSO, 298 K): d194.5 (C1), 162.6 (d,1J = 247 Hz, C30,50), 136.1 (t, 3J = 8 Hz, C10), 112.1 (d, 2J = 17 HzC20,60), 110.1 (d, 2J = 15 Hz C40), 58.4 (C2), 30.6 (N-Me), 15.0 (C3).

4.2.2. 3,5-Dichloromethcathinone.HCl

In the observed 1H and 13C NMR spectra the chemical shiftswere consistent with those observed in other methcathinonederivatives [11,16]. The aromatic region of the 1H NMR exhibitstwo resonances, a doublet (d 8.03 ppm) and triplet (d 7.97 ppm),with integral intensities of 2:1 respectively, sharing a mutual 4JHH

coupling of 1.9 Hz; confirming symmetrical meta-substitution inthe ring.

1H (400 MHz, d6-DMSO, 298 K) d 8.03 (2H, d, J = 1.9 Hz, H20,60),7.97 (1H, t, J = 1.9 Hz, H40), 5.26 (1H, q, J = 7.1 Hz, H2), 2.57 (3H, s,N-Me), 1.43 (3H, d, J = 7.1 Hz, H3).

13C (100 MHz, d6-DMSO, 298 K) d 194.6 (C1), 136.1 (C10), 135.1(C30, 50), 133.5 (C40), 127.3 (C20, 60), 58.2 (C2), 30.5 (N-Me), 14.9(C3).

inone (c) N-acetyl-3,5-dichloromethcathinone and (d) suspected N-acetyl-3,5-

Fig. 7. ATR-FTIR spectra for (a) 3,5-difluoromethcathinone hydrochloride (b) suspected 3,5-difluoromethcathinone hydrochloride and the compound tentatively identified as

11 (c) 3,5-dichloromethcathinone hydrochloride and (d) suspected 3,5-dichloromethcathinone hydrochloride.

S. Davis et al. / Forensic Science International 217 (2012) 139–145144

4.3. Infrared spectroscopy

Infrared analysis provides a rapid identification for organiccompounds due to their unique infrared spectra [20]. Bothcondensed and vapour phase infrared spectra have been shownto distinguish between the isomers of various methcathinoneanalogues and it is also known to be an alternative to derivatisationwhen this technique is unsuitable [12,16,21,22].

As the submitted sample of the 3,5-difluoromethcathinonecontained an impurity suspected to be compound 11, clear

Fig. 8. Vapour phase infrared spectra for (a) 3,5-difluoromethcathinone, (b) suspected

dichloromethcathinone.

differences could be observed in the condensed phase infraredspectra between the submitted and synthesised samples (Fig. 7).The ability to separate the compounds via GCIRD, however,enabled the vapour phase infrared spectra of these samplesto be compared (Fig. 8). From this it can be demonstratedthat the vapour phase infrared spectra between the twocompounds displays a high level of congruency. Both thevapour phase (Fig. 8) and the condensed phase infrared spectra(Fig. 7) for 3,5-dichloromethcathinone shows they are in strongagreement.

3,5-difluoromethcathinone, (c) 3,5-dichloromethcathinone and (d) suspected 3,5-

S. Davis et al. / Forensic Science International 217 (2012) 139–145 145

5. Conclusions

This study provides the synthesis and structural elucidation ofthe cathinone analogues 3,5-difluoromethcathinone 5 and 3,5-dichloromethcathinone 6, which have not previously beenreported in the literature. As the ‘Legal High’ market evolves itis likely that we will continue to see a greater number of variationsmade to existing illicit drugs. It can be determined from the datathat the submitted samples were 3,5-difluoromethcathinone and3,5-dichloromethcathinone. We present the MS data for thesecompounds and their N-acetyl derivatives. We have also providedthe 1H and 13C data, and both vapour and condensed phase IRspectra. These analytical results will enable the rapid identificationof these compounds if encountered by other forensic laboratoriesor law enforcement agencies. We have also presented the tentativeidentification of an isomeric by-product, which may act as amarker for similar halogenated cathinone analogues.

Acknowledgments

The authors would like to acknowledge the support provided bythe Clinical and Statewide Services (CASS) research committee andfunding from the QHFSS Cabinet Research and Development Fundfor this study.

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