Unexpected identification and characterization of a cathinone precursor in the new psychoactive substance market: 3′,4′-methylenedioxy-2,2-dibromobutyrophenone

Journal Pre-proof Unexpected identification and characterization of a cathinone precursor in the new psychoactive substance market: 3 ,4 -methylenedioxy-2,2-dibromobutyrophenone Sergio Armenta, Cristina Gil, Mireia Ventura, Francesc A. Esteve-Turrillas

PII:

S0379-0738(19)30455-4

DOI:

https://doi.org/10.1016/j.forsciint.2019.110043

Reference:

FSI 110043

To appear in:

Forensic Science International

Received Date:

9 September 2019

Revised Date:

30 October 2019

Accepted Date:

31 October 2019

Please cite this article as: Armenta S, Gil C, Ventura M, Esteve-Turrillas FA, Unexpected identification and characterization of a cathinone precursor in the new psychoactive substance market: 3 ,4 -methylenedioxy-2,2-dibromobutyrophenone, Forensic Science International (2019), doi: https://doi.org/10.1016/j.forsciint.2019.110043

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.

Unexpected identification and characterization of a cathinone precursor in the new psychoactive substance market: 3′,4′-methylenedioxy-2,2dibromobutyrophenone Sergio Armenta 1, Cristina Gil 2, Mireia Ventura 2, Francesc A. Esteve-Turrillas 1* 1

Department of Analytical Chemistry, University of Valencia, 50th Dr. Moliner St., 46100 Burjassot, Spain 2

Energy Control. Asociación Bienestar y Desarrollo, 384th Independencia St., 08041 Barcelona, Spain

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*Corresponding author Tel.: (+34)963544004; e-mail address: [email protected]

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Graphical abstract

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Highlights  A case report of a mislabelled product sold as ketamine.  The substance has been identified as 3′,4′-methylenedioxy-2,2dibromobutyrophenone.  A full characterization has been performed by FTIR, GC-MS, HRMS, and NMR techniques.  The substance is a precursor or intermediate compound in the synthesis of cathinones. Abstract 3′,4′-methylenedioxy-2,2-dibromobutyrophenone has been identified and fully characterized in a sample obtained from an anonymous consumer acquired as ketamine through the 1

Internet market. The substance has been deeply characterized by using standard and high performance analytical techniques such as: attenuated total reflectance-infrared spectroscopy, gas chromatography–mass spectrometry, high-resolution mass spectrometry, elemental analysis, and nuclear magnetic resonance, including1H,

13

C, distortionless enhancement by

polarization transfer, two dimensional homonuclear 1H-1H correlation spectroscopy, and 1H-13C heteronuclear

single-quantum

correlation

spectra.

3′,4′-methylenedioxy-2,2-

dibromobutyrophenone is a precursor or intermediate in the synthesis of several synthetic

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cathinone derivatives, such as pentylone and methylenedioxy pyrovalerone. It is expected that 3′,4′-methylenedioxy-2,2-dibromobutyrophenone does not act as psychoactive substance through disruption nor dysregulation of central and peripheral nervous systems, due to the

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absence of the characteristic amine group of cathinone derivatives. Although it cannot be

considered a trend in new psychoactive substances consumption, the presence in the market

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and the unknown toxicity of this substance makes it a relevant fact.

Keywords New psychoactive substances; counterfeit; full characterization; attenuated total

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reflectance-infrared spectroscopy; nuclear magnetic resonance spectroscopy

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1. Introduction New psychoactive substances (NPS) were defined by the United Nations Office on Drugs and Crime (UNODC) as substances of abuse which have similar effects to drugs under international control conventions, but not controlled yet [1]. Generally, NPS present similar molecular backbone to their illicit counterparts, differing in one or several functional groups attached to the chemical scaffold [2]. A characteristic of the NPS market is that it is very dynamic and the emergence of new substances is a usual fact, from which some of them persist on the market

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for years, while others disappear over time. The range of products is continually evolving to evade the changes in the control of NPS. According to data of the European Monitoring Centre for drugs and drug addiction, by the end of 2018 the European Early Warning System (EU EWS)

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was routinely monitoring over 730 substances. In 2018, 55 NPS were formally notified for the

first time. The largest substance categories monitored by the EU EWS are the synthetic

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cannabinoids (45 %) and synthetic cathinones (33 %). NPS are usually sold in the Internet as powders supplied in zip-lock plastic bags with little indication of the required dose and labelled

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as ‘research chemicals, strictly not for human consumption’, ‘plant food’ or ‘bath salts’ [3]. Some of these substances are also being sold by dealers through the dark web [4,5], being the

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perception of the users that these drugs are pure and safe [6]. Moreover, insufficient or no labelling of these illicit substances does not provide any information about the active

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constituents, and in some cases the included information is very limited and often inaccurate [7,8,9]. Typical examples are the misleading labeling using generic brand names, like “spice” or

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“K2” [10] or mislabeling by selling one compound as another [11,12]. Mislabelled products may also appear in the market as consequence of legislative changes to control certain substances, by changing the product package but not the content [13]. In this paper, a case report in which the identity of the compound sold is different by that reported

by

the

manufacturer

has

been

assessed.

3′,4′-methylenedioxy-2,2-

dibromobutyrophenone was identified and fully characterized in a sample obtained from an

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anonymous consumer through the Internet and sold as ketamine. The identification and characterization of nature and purity of this compound was performed by attenuated total reflectance (ATR) infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC– MS), liquid chromatography diode array detector (LC-DAD), high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and elemental analysis. It has been previously published that 3′,4′-methylenedioxy-2,2-dibromobutyrophenone is a precursor or intermediate in the synthesis of several synthetic cathinone derivatives, such as

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pentylone and methylenedioxy pyrovalerone (MDPV) [14]. The synthesis of both cathinone derivatives includes the formation of a brominated alkylphenone precursor at the α‐position. It has been demonstrated that together with α‐brominated products, an extensive formation of

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α,α‐dibrominated intermediates occurs, being not possible the isolation of the mono‐ brominated intermediates. Given its chemical structure differences to dopamine and

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serotonin, it is expected that 3′,4′-methylenedioxy-2,2-dibromobutyrophenone does not act as stimulant through disruption nor dysregulation of central and peripheral monoamine systems

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2. Materials and methods

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[15]. However, no data regarding toxicity of this substance has been reported yet.

2.1. Samples and reagents

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The sample, consisting of approximately 0.5 g of a fine white powder, was submitted by an anonymous consumer to Energy Control for analysis. According to the information provided by

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the consumer, it was purchased from the Internet as ketamine, but no information was received about the consumption or psychoactive effects of this product. Energy Control is a project based on risk reduction, belonging to the Spanish non‐governmental organization Asociación Bienestar y Desarrollo. Energy Control offers an anonymous drug testing service. Additional information about Energy Control can be seen elsewhere [16].

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Organic solvents and buffer constituents for sample dilution and mobile phase preparation were obtained from Scharlab (Barcelona, Spain). Deuterated chloroform (CDCl3, 99.96 % purity) was obtained from Merck (St. Louis, MO, USA).

2.2. Fourier–transform infrared spectroscopy A SpectrumTwo Fourier-transform infrared (FTIR) spectrometer, equipped with a DTGS detector, was obtained from Perkin-Elmer (Waltham, MA, USA) for FTIR spectra

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measurements. Five milligrams of sample were analyzed by a one-reflection ATR diamond disk. Sample spectrum was collected in the region between 4000 and 400 cm-1, with a resolution of 4 cm-1, averaging 25 scans, using the same conditions for background setting. Sample spectrum was compared to those obtained for NPS from the IR library of the Scientific Working Group

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for the analysis of seized drugs (SWGDRUG) Version 2.0 (February 8th, 2019) containing 590

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spectra in OPUS format [17].

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2.3. Gas chromatography–mass spectrometry

A 7890A GC–MS and a 5975Cinert XL EI/CI MSD triple axis single quadrupole detector,

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obtained from Agilent Technologies (Santa Clara, CA, USA), were employed for sample analysis. An Agilent HP-5ms capillary column (30 m × 0.25 mm i.d., film thickness 0.25 µm) was

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employed for chromatographic separation. Five milligrams sample was dissolved in acetone and 1 µL solution was injected in the splitless mode at 250 °C, using 1 mL/min helium as

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carrier. Oven temperature program started at 150 °C for 1 min, increased at 10 °C/min to 250 °C, and finally held 5 min at 250 °C. Transfer line and ion source temperatures were 300 and 250 °C, respectively. An electron voltage at 70 eV was employed for electron impact (EI) ionization. Acquisitions were taken using a m/z range from 40 to 450. The obtained EI-MS spectrum for the analyzed sample was compared with those of the SWGDRUG spectra Version 3.5 (May 20th, 2019) containing 3047 spectra in Agilent format [18].

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2.4. Liquid chromatography–diode array detection An Agilent 1100 Series liquid chromatography with a diode array detector (DAD) system was employed for the assessment of sample purity. A Kromasil C18 (250 x 4.6 mm i.d., 5.0 μm particle diameter) column, from Scharlau (Barcelona, Spain), was employed for sample separation, using a mobile phase gradient of methanol (A) and 0.05 M phosphate buffer, pH 7.2 (B) at a flow rate of 1 mL/min. The employed gradient started at 20 % A, increased to 90 %

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A in 20 min, and it was maintained at 90 % A for 5 min. Ultraviolet (UV) absorption spectrum was acquired scanning from 200 to 400 nm. Five milligrams sample was diluted in methanol

and analyzed using 20 µL as injection volume. The relative UV spectral purity of the sample

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was calculated using the area normalization criterion [19].

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2.5. High-resolution mass spectrometry

A TripleTOF™ 5600 LC/MS/MS System, with an electrospray ionization (ESI) source, from AB

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SCIEX (Redwood City, CA, USA) was employed for acquisition of HRMS spectra. Five milligrams sample diluted in methanol were analyzed by direct infusion. Experimental conditions are as

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follow: positive ionization mode, nitrogen as ion source gas, 35 psi ion source gas 1 and 2, 25 psi curtain gas pressure, 400 °C source gas temperature, and 5500 V ion spray voltage.

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PeakView software, from AB SCIEX, was employed for data treatment. Sample was dissolved in methanol:10 mM ammonium formate in water (80:20 %, v/v) and introduced at a 0.1 mL/min

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flow rate.

2.6. Nuclear magnetic resonance spectroscopy A Bruker AVIII spectrometer, equipped with a 5 mm direct probe, from Bruker (Billerica, MA, USA) was employed for acquisitions of NMR spectra. 1H spectrum was acquired at 300.13 MHz, 298 K with a direct observation, 30° pulse and 16 scan, and TRAF resolution enhancement was

6

applied without linebroadening. The obtained chemical shifts (δ, ppm) were referenced to tetramethylsilane.

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C NMR and distortionless enhancement by polarization transfer (DEPT)

spectra were acquired at 75 MHz by direct observation 30° angle and 512 scans. Two dimensional homonuclear 1H-1H correlation spectroscopy (COSY) experiment was carried out with gradient selection. 1H-13C heteronuclear single-quantum correlation (HSQC) spectroscopy experiments were carried out at double insensitive nuclei enhanced by polarization transfer (INEPT), in-phase and TPPI-Eco-Antieco gradient selection. Heteronuclear multiple bond

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correlation (HMBC) was acquired with 16 scans for direct dimension and 256 scans for indirect dimension at 400.913 MHz. Mnova 12 software, from Mestrelab Research S.L. (Santiago de Compostela, Spain), was employed for NMR data treatment. Five milligrams sample was

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dissolved in CDCl3 for NMR spectra acquisitions.

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2.7. Elemental analysis

Carbon, hydrogen, nitrogen, and sulfur content were determined by a CE Instruments CHNS

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1100 Elemental Analyser (Wigan, UK). Five milligram of sample were introduced, without any additive, to a silver capsule for elemental analysis. Sulfanilamide, obtained from Carlo Elba

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(Sabadell, Spain), was employed for instrument calibration.

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3. Results and discussion

3.1. Infrared spectroscopy

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The ATR-FTIR spectrum obtained for the sample (see Figure 1) was not accurately identified by the SWGDRUG library. Results obtained from the library search provided a high similarity with synthetic

cathinone

compounds,

such

as:

butylone

HCl,

3,4-methylenedioxy-α-

pyrrolidinobutiophenone (3,4-MDPBP) HCl, N-ethylpentylone HCl, 3-desoxy-3,4-MDPV HCl, and dibutylone HCl, with match values higher than 740. It suggest that the molecular structure of

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the analyzed sample highly correlated to a 3,4-methylenedioxy-cathinone compound, probably with alkylated chains and/or a pyrrolidine group as amine substituents. The absence of absorption bands at approximately 3226 cm-1 indicates that the compound does not present NH groups in its structure [20]. Moreover, it was also not present in the spectrum the NH2+ stretching bands that traditionally appears between 2250-2700 cm-1, for hydrochlorides [21]. Additionally, the sharp and strong band appearing at 600 cm-1 can be due to C-Br stretching (500-700 cm-1).

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In summary, although the information provided by the ATR-FTIR analysis was not conclusive, it suggested that the seized sample could be a 3,4-methylenedioxy cathinone derivative without the NH group. However, additional information must be given in order to confirm this

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3.2 Gas chromatography–mass spectrometry

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preliminary hypothesis.

The obtained GC-MS chromatogram provided two peaks at 9.8 and 11.4 min, providing the

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same EI-MS spectra (see Figure 2). The presence of two signals may correspond mainly to the presence of mixtures or in a minor extent due to a decomposition of the analyte in the GC

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injector. The obtained spectra show ion fragments at m/z 149.0 and 121.0, that corresponds to the typical fragmentation of 3,4-methylenedioxy-N-alkylated cathinone derivatives [22].

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Nevertheless, the obtained spectrum was not accurately identified by the SWGDRUG library, giving low match values (lower than 45) with several 3,4-methylenedioxy-N-alkylated

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cathinones. Moreover, in Figure 2 it can be seen the m/z fragment 65, typical of brominated and dibrominated 3,4-methylenedioxy derivative precursors.

3.3. Purity of seized sample The purity of the sample was calculated using the peak area normalization criterion, based on the calculation of individual peak areas as a percentage of the total area of all the peaks in the

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LC–DAD chromatogram. As it can be seen in Figure SM1 of the electronic supplementary material, a sharp peak corresponding to the analyte under study and very small peaks due to impurities were observed at 220 nm. To verify the absence of co-eluting compounds it is necessary to ensure the purity of the peak. If a peak is pure, the whole UV-visible spectra acquired during the peak elution should be identical, and the results found by comparison of all the spectra obtained during a peak elution should be very close to a perfect match (100%). The calculated peak purity hit was 951, with a peak symmetry of 0.92 and a width of 0.32 min

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and a retention time of 13.71 min. The resulting sample purity, calculated using the normalized area criteria, was higher than 95.0 %. Thus, the obtained results indicated the high purity of

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the seized sample.

3.4 High-resolution mass spectrometry

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Sample was analyzed by HRMS providing the low and high energy spectra shown in Figure 3. Low energy spectrum provided a multiple signal at m/z 364.9213, with the typical isotopic

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pattern of a dibrominated compound. The elemental composition of the protonated molecule ion was set as C12H12Br2O3, with 6 unsaturations and a mass error of +2.2 ppm. Other potential

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molecular structures with the same weight were discarded due to the absence of bromines in their structure. The absence of any nitrogen atoms totally discards the hypothesis of a

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cathinone compound.

MS spectra obtained at high energy provided ions at m/z 364.9170 282.9931, 254.9990,

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176.0808, and 149.0210, corresponding to the C12H12Br2O3 molecular ion and the C12H12BrO3, C10H8BrO3, C10H8O3, and C8H5O3 fragments, respectively. Justification of fragments can be also seen in Figure 3B. The proposed elemental composition, together with the number of unsaturations and the fragmentation pattern, confirms a 3,4-methylenedioxy-benzaldehyde (piperonal) derivative

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with a 4 carbon alkylated chain (linear or branched) and 2 bromine atoms. Thus, NMR is required for the confirmation of the position of bromine substituents.

3.5. Nuclear magnetic resonance 1

H,

13

C, DEPT, COSY, and HSQC spectra were acquired for the analyzed samples in order to

assign chemical shifts to the proposed molecule structure (see Figures 4 and 5). The structure of a piperonal derivative was confirmed by the obtained spectra, having

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chemical shifts unambiguously attributed as shown in Table 1. The obtained aromatic proton shifts were 8.05, 7.84, and 6.68 ppm for the phenyl three substituted phenyl group and a

singlet at 6.07 ppm corresponded to the 3,4-methylenedioxy group. 13C NMR spectra showed a typical piperonal pattern with aromatic shifts in the 102-152 ppm range and ketone carbon

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C chemical shifts were compared to those obtained for other 3,4-methylenedioxy-

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and

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shift at 186.7 ppm. All these signals were confirmed by COSY and HSQC spectra. Moreover, 1H

cathinone derivatives [14], providing comparable chemical shifts.

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Regarding the alkylated chain, 1H and 13C NMR spectra confirms the presence of a 4-C linear

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chain with two bromide atoms in the carbon linked to the ketone group.

3.6. Elemental Analysis

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The proposed structure was confirmed by NCHS elemental analysis with the presence of 40.6 % C, 3.3 % H, and N and S contents lower than limit of quantification of the technique (0.2 % N

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and 0.3% S), being the theoretical percentages of C12H12Br2O, 39.9 %C and 3.3 % H. Thus, the absence of nitrogen was confirmed and the obtained C/H ratio (12.3) is compatible by the proposed elemental composition of the sample (12.1).

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4. Conclusions In this case report, 3′,4′-methylenedioxy-2,2-dibromobutyrophenone was identified and fully characterized in a sample obtained from an anonymous consumer sold as ketamine through the Internet market. The substance has been deeply characterized by using standard and high performance analytical techniques such as: ATR-FTIR, GC-EI-MS, HRMS, NMR, including 1H, 13C, DEPT, COSY, and HSQC, and elemental analysis. This study confirms the heterogeneity of NPS market, where in some cases unexpected substances can be purchased for users. In this

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particular case, the presence of a precursor for the synthesis of cathinone derivatives has been identified, which is expected to show a no stimulant effect on the user through disruption nor dysregulation of central and peripheral monoamine systems, and an absolutely unknown

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toxicity. In spite of the present study cannot be considered a new trend in the current NPS market, the occurrence of unexpected compounds in mislabeling products, with consequent

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unknown toxicity and effects, makes it a relevant fact.

Ethical approval

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CRediT authorship contribution statement All authors have participate in the work to take public responsibility for the content, including Conceptualization, Methodology, Validation, Formal analysis, Investigation, Resources, Writing, Visualization, and Supervision.

This article does not contain any studies with human participants or animals performed by any

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of the authors.

Conflict of interest The authors have no financial or other relations that could lead to a conflict of interest.

Acknowledgements: Authors gratefully acknowledge the technical support from M. Sales Galletero, Isabel Solana and Salomé Laredo from the SCSIE of the University of Valencia.

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Electronic supplementary information

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Supplementary information can be found in the online version, at

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35 (2014) 20-25. [13] C.S. Johnson, B.R. Copp, A. Lewis, New psychoactive substances detected at the New Zealand border, Drug Test. Anal. 11 (2019) 341-349.

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of ocfentanil as an adulterant in heroin, Int. J. Drug Policy 40 (2017) 78–83. [17] Scientific working group for the analysis of seized drugs (SWGDRUG) IR library, Version

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2.0 (February 8th, 2019), http://www.swgdrug.org/ir.htm

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[20] R.A. Heacock, L. Marion, The infrared spectra of secondary amines and their salts, Can. J. Chem. 34 (1956) 1782-1795. [21] R.T. Conley, Infrared Spectroscopy, 2nd edn. Allyn and Bacon Inc., Boston (1972). [22]

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Legend of figures

Fig. 1 Attenuated total reflectance-Fourier-transform infrared spectroscopy spectra obtained for

the

analyzed

sample

and

methylenedioxypyrrolidinobutiophenone

related HCl,

compounds:

butylone

N-ethylpentylone

HCl,

HCl,

3,4-

3-desoxy-3,4-

methylenedioxy pyrovalerone HCl, and bk-DMBDB HCl.

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10

Butylone HCl match: 746

9

-p re

8

3,4-MDPBP HCl match: 752

5

3,4-MDPV HCl match: 764

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4

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N-ethylpentylone HCl match: 761

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6

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ATR units (a.u.)

7

3

2

1

Dibutylone HCl match: 778

Sample

0

16 4000 3500 3000 2500

1800

1600

1400

1200

Wavenumber (cm-1)

1000

800

600

Fig. 2 Total ion current chromatogram (a), and mass spectrum (b) obtained for the analyzed sample by gas chromatography–electron impact–mass spectrometry.

9000000 8000000 7000000 6000000 5000000 4000000 3000000 2000000 1000000 0

11.4

9.8

5

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Intensity (a.u.)

a)

10

15

b) 3500000

-p

149

3000000

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2500000 2000000

1500000

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Intensity (a.u.)

20 Time (min)

1000000 65

500000

121

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0

75

100

125

150

170

189

210

230 250 m/z

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50

Fig.3 Low (a) and high (b) energy high-resolution mass spectrometry spectra of the analyzed

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sample. Insets show the corresponding m/z error values.

a)

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3.0E+04 364.9213 (100.0) 1.9 ppm

Intensity

2.5E+04 2.0E+04 362.9234 (57.2) 2.2 ppm

1.5E+04

366.9193 (57.2) 1.6 ppm

1.0E+04

365.9244 (18.0) 1.2 ppm 363.9266 (9.4) 1.7 ppm

5.0E+03

367.9225 (9.5) 1.3 ppm

0.0E+00 335

345

355

365

375

m/z

b) 3.0E+04 254.9990

256.9781

-p

2.0E+04 1.5E+04 1.0E+04 149.0210 176.0808

5.0E+03

150

364.9170

282.9931

0.0E+00 100

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Intensity

2.5E+04

385

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325

200

250

300

350

400

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m/z

Fig. 4 1H (300 MHz) (a), and two dimensional 1H-1H homonuclear correlation spectroscopy

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(COSY) (b) nuclear magnetic resonance spectra.

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2H (s) 6.07 ppm 1H (d) 6.86 ppm

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1H (dd) 8.05 ppm

1H (d) 7.84 ppm

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HDO

CDCl3

a)

2H (m) 2.63 ppm

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b)

3H (t) 1.06 ppm

2H (d) 1.76 ppm H12 (CH3) H11 (CH2)

H10 (CH2)

H7 (CH2)

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H5 (CH)

H2 (CH)

H6 (CH)

Fig. 5 13C nuclear magnetic resonance spectroscopy (75 MHz) (a), distortionless enhancement by polarization transfer (DEPT) (135 ˚) (b) and 1H-13C heteronuclear single-quantum correlation spectroscopy (HSQC) (c). 19

a)

107.6 (C5, CH) 128.0 (C6, CH)

151.9 (C4, C)

102.0 (C7, CH2)

48.0 (C10, CH2)

20.9 (C11, CH2) 13.5 (C12, CH3)

66.6 (C9, C)

126.4 147.2 (C3, C) (C1, C)

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186.7 (C8, C)

111.2 (C2, CH)

13.5 (C12, CH3)

b) 111.2 (C2, CH) 107.6 (C5, CH)

lP

102.0 (C7, CH2)

re

-p

128.0 (C6, CH)

20.9 (C11, CH2)

na

48.0 (C10, CH2)

Jo

ur

c)

20

21

ro of

-p

re

lP

na

ur

Jo

Table 1 Data for the identification and characterization of the seized sample by: Attenuated total reflectance-Fourier-transform infrared spectroscopy (ATR–FTIR), liquid chromatography-diode array detector (LC-DAD), electron ionization-mass spectrometry (EI–MS), high-resolution mass spectrometry (HRMS), proton (1H) and carbon (13C) nuclear magnetic resonance (RMN) spectroscopy, and elemental analysis.

LC-DAD EI-MS ESI-HRMS

Absorbance maximums (nm) Fragmentation (m/z, % intensity) [MH]+ exact mass (m/z) Protonated molecular mass (m/z, ppm) δ (ppm, 300 MHz)

1

H NMR

13

δ (ppm, 75 MHz)

Elemental analysis

% obtained (theoretical)

186.7 (C8, C) 151.9 (C4, C) 147.2 (C3, C) 128.0 (C6, CH) 126.4 (C1, C) 111.2 (C2, CH) 107.6 (C5, CH) 102.0 (C7, CH2) 66.6 (C9, C) 48.0 (C10, CH2) 20.9 (C11, CH2) 13.5 (C12, CH3) N < 0.2 (0.0) C 40.6 (39.9) H 3.3 (3.3) S < 0.3 (0.0)

Jo

ur

na

lP

re

C NMR

Values 2964, 1167, 1609, 1501, 1435, 1345, 1257, 1101, 1032, 929, 891, 828, 602 200, 240, 290, 328 149.0 (100), 121.0 (15), 85.0 (10) 362.9234 (57), 364.9213 (100), 366.9193 (57) 362.9226 (+2.2) 8.05 (dd, J=8.4, 1.9 Hz, 1H, C6) 7.84 (d, J=1.8 Hz, 1H, C2) 6.86 (d, J=8.4 Hz, 1H, C5) 6.07 (s, 2H, C7) 2.68-2.57 (m, 2H, C10) 1.86-1.67 (m, 2H, C11) 1.06 (t, J=7.4 Hz, 3H, C12)

ro of

Parameter Main bands (cm-1)

-p

Technique ATR-FTIR

22