Mix of new substances psychoactive, NPS, found in blotters sold in two Colombian cities

Journal Pre-proof Mix of new substances psychoactive, NPS, found in blotters sold in two Colombian cities Catrin Y. Mendoza-Valencia (Conceptualization) (Methodology) (Validation) (Investigation) (Writing - original draft), Diana Jazm´ın ˜ Gaviria (Investigation) (Supervision) (Writing - review and Marino ˜ Reyes (Supervision), Fabian editing) (Visualization), Nancy Patino ´ Lopez-Vallejo (Writing - review and editing), Alvaro Emilio ´ Sarmiento Gutierrez (Data curation) (Software) (Validation), Daniel Trespalacios Rodr´ıguez (Methodology) (Validation)

PII:

S0379-0738(19)30381-0

DOI:

https://doi.org/10.1016/j.forsciint.2019.109969

Reference:

FSI 109969

To appear in:

Forensic Science International

Received Date:

24 June 2019

Revised Date:

20 September 2019

Accepted Date:

27 September 2019

˜ Gaviria DJ, Patino ˜ Reyes N, Please cite this article as: Mendoza-Valencia CY, Marino ´ Trespalacios Rodr´ıguez D, Mix of new substances ´ Lopez-Vallejo F, Sarmiento Gutierrez AE, psychoactive, NPS, found in blotters sold in two Colombian cities, Forensic Science International (2019), doi: https://doi.org/10.1016/j.forsciint.2019.109969

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Mix of new substances psychoactive, NPS, found in blotters sold in two Colombian cities

Author names:

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Mendoza-Valencia*, Catrin Y. Master in Toxicology, Faculty of Medicine, Universidad Nacional de Colombia.

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Mariño Gaviria, Diana Jazmín Toxicologist, Toxicology Laboratory Instituto Nacional de Medicina Legal y Ciencias Forenses Regional Bogota. Calle 7 A # 12 A – 51 Bogotá, 110321, Colombia. E-mail: [email protected]

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Lopez-Vallejo Fabian

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Patiño Reyes, Nancy Professor of the Department of Toxicology, Faculty of Medicine, Universidad Nacional de Colombia. Universidad Nacional de Colombia, Carrera 45 # 26 – 85 Edif. Uriel Gutiérrez, 111321 Bogotá, Colombia. E-mail: [email protected]

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Professor of the Department of Chemistry, Faculty of Sciences, Universidad Nacional de Colombia. Universidad Nacional de Colombia, Carrera 45 # 26 – 85 Edif. Uriel Gutiérrez, 111321 Bogotá, Colombia. [email protected]

Sarmiento Gutiérrez, Álvaro Emilio

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Coordinator of the Forensic Sciences Regional Group of the Instituto Nacional de Medicina Legal y Ciencias Forenses (Regional Norte), Carrera 23 # 53 -56 Barranquilla, 080012, Colombia. E-mail: [email protected]

Trespalacios Rodríguez, Daniel Forensic expert of the Toxicology Laboratory. Instituto Nacional de Medicina Legal y Ciencias Forenses (Regional Norte). Carrera 23 # 53 -56 Barranquilla, 080012, Colombia. E-mail: [email protected]

*Corresponding author: Tel.: +0057 301 202 0566 E-mail address: [email protected] Universidad Nacional de Colombia, Carrera 45 # 26 – 85 Edif. Uriel Gutiérrez, 111321 Bogotá, Colombia

HIGHLIGHTS

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First time the detection of DOB in blotters seized in Colombia is reported. The blotters sold as LSD in at least two Colombian cities are mixtures of NPS known as DOB, MDMA, and 25I-NBOMe Mixtures of NPS were detected in the same blotter with traditional drugs of abuse. Caffeine and ketamine are used, in some cases, as adulterants in the sale of blotters. Mixtures of NPS in the same dose can cause interactions or adverse effects not yet investigated.

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Abstract

The new psychoactive substances (NPS) in Colombia are detected by national authorities,

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in blotters strip, in different circumstances and places: airports, music concerts, discos and parks. Blotters are marketed as LSD and cause several cases of intoxication and death in

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some consumers: due to acute intoxication or when mixed with other drugs and may have different effects on the central nervous system (CNS). This study was conducted to research into and identify the chemical composition of the drugs impregnated in the blotters sold in

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two Colombian cities. This research provides the analysis of 70 doses coming from forensic cases of the Colombian Attorney General's Office in Bogota and from the Laboratory of Narcotics of the Colombian National Institute of Legal Medicine and Forensic Sciences (North Headquarter) in Barranquilla. Mixtures of drugs, such as DOB, 25I-NBOMe, MDMA and 25I-NBOMe imine were found within the blotters through gas

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chromatography coupled to mass spectrometry (CG-MS); these drugs are classified by international authorities as NPS belonging to the phenylethylamines group. The results clearly warn about a growing public health problem in the country.

Keywords: GC-MS, Phenylethylamine, blotters, MDMA, DOB, 25I-NBOMe, NPS, CNS

1. Introduction. In Colombia, NPS refer to new drugs being introduced to the market. These include, in addition to the new substances, any change in the presentation, pattern of use, purity, or presence of adulterants, which may imply a threat to public health and are subject to analysis by the Early Warning System (SAT, for its acronym in Spanish) [1]. According to the NPS detection report, between 2009 and 2017, 28 NPS were detected in Colombia[2] and 803 around the world, detected in more than 100 countries [2] [3]. Their toxicological effects are unknown [4], since the substituents of their scaffolds are frequently modified;

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making detection and control even more difficult, as they avoid international security

systems. This has paved the way for drug dealers to market globally, without any kind of

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control, by selling those drugs as "legal highs" or "herbal highs" in online sales[5]. Within these 28 new psychoactive reported substances, there are substances of the group known as

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phenylethylamine (see Figure 1), which are sold in blotters strips. These blotters are absorbent papers, with brightly colored designs and eye-catching motifs for any consumer

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group. It should be noted that one of the sales strategies is the design of the blotter, which

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shows the effect that the consumer will experience.

It has been difficult to detect phenylethylamines through colorimetric methods. For this

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purpose, the authorities use the gas chromatography-mass spectrometry (CG-MS) technique to accurately identify any substance with its the references standards; in the event, where the laboratories do not have the reference material of any NPS, the identification must be supported by the equipment library. For NPS, the use of the SWGDRUG MS library [6] is recommended, as it contains most chemical structures of NPS and its isomers, which have

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been detected worldwide. The identification of the NPS in Colombia poses a major challenge to the healthcare system due to the implicit toxicity of these substances and the ignorance about their adverse effects, and mainly because they are sold as LSD [7,8]. The reported cases in Colombia constitute reliable evidence of abuse and consumer cheating [2,9]. For this reason, in this work we identify the composition of blotters sold as LSD in Barranquilla and Bogotá, to warn health authorities about NPS in the country and put care

centers on alert [10]. Additionally, we present the most relevant qualitative findings of the studied blotters.

2. Materials and Methods 2.1. Materials and reagents The material used in the study was seventy doses of blotters strips with printed illustrations

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from the cities of Bogotá and Barranquilla (see Figure 2).

The reference and standard solvents used were: 3,4 - Methylenedioxymethamphetamine

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hydrochloride, MDMA, (99 %); 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-

methoxybenzyl)ethanamine hydrochloride, 25C-NBOMe, (99.441 %); 2-(4-bromo-2,5-

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dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride, 25B-NBOMe, (99.007 %); 2-(4-iode-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride, 25I-

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NBOMe, (99.911 %); 4-bromo-2,5-dimethoxyphenylethylamine hydrochloride, 2C-B, (99 %); 4-bromo-2,5-dimethoxyamphetamine hydrochloride, DOB, (99 %); (6aR,9R)-N, Ndiethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide, LSD, (99

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%) were purchased from Lipomed AG (Arlesheim, Switzerland); 4-choro-2,5dimethoxyamphetamine hydrochloride, DOC, (100 %) was purchased from Cayman Chemical Company (Ann Arbor, Michigan, USA); absolute ethanol (99.8 %); tetracosane

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(99 %) from Sigma Aldrich (Milan, Italy) as internal standard (ISTD).

2.2. Sample preparation

The approximate dimensions of the blotters containing one dose were 0.7 cm * 0.7 cm. The complete table of blotters strips (3.5 cm * 3.5 cm) had 25 doses. The doses were randomly coded with the following acronym: M1, where M is the sample and 1 is the number of the dose under study, as shown in Figure 3.

The blotter strip was cut and put into a vial (previously labeled) containing 1 mL of ISTD at 100 ppm dissolved in ethanol, then heated to 30 °C, and sonicated for 10 min. 2.3. Instrumentation The sample was injected directly into a gas chromatography (model Trace 1300, Thermo Scientific) with TRIPlus RSH coupled to a mass spectrometer (model ISQ LT Single Quadrupole, Thermo Scientific) system. The separation was performed in a capillary

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column: 5% phenyl-95% methylpolysiloxane Rtx-5 (30 m * 0.25 mm D.I.* 0.25 µm film

thickness). The injector temperature was set at 270 °C (splitless mode). 1.0 µL was used as

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injection volume. The carrier gas was helium with a flow rate of 1.0 mL/min. The oven

was initially heated to 150 ºC and set to 25 ºC/min, then to 200 ºC and set to 25 ºC/min; and

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finally, to 300 ºC and set to speed of 15 ºC/min with this temperature for 3 minutes. Data acquisition was performed in SCAN mode (28-500 m/z). The electron impact ionization in

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the mass spectrometer was performed at a 70 eV. The identification of the NPS found in the blotters strips were achieved by comparing the retention times and the characteristic

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fragments of the NPS are those with the reference standards used and the ion pattern of the SWGDRUG MS library with a match of 98%. Data acquisition and processing were carried

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out by Chromeleon software (version 7.1). The running time was 23.00 minutes.

Figure 4 shows the chromatographic profile of the 8 substances (concentration of 10 µg/mL) used in the analytical method for the analysis of seized blotters and the internal standard (tetracosane). They were chosen according to the seizure record of NPS in the two

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laboratories. The separation of each of them and their retention times is observed in the following order of detection: MDMA (3.984), DOC (5.545), 2C-B (6.497), DOB (6.531), 25C-NBOMe (15.347), 25B-NBOMe (15.928), 25I-NBOMe (16.636) and LSD (20.333). The detection limit (LOD) of the method was 7 µg/mL and for the drug DOC 5 µg/mL. It was determined from different dilutions of the analytes until a minimum detectable and integrable signal was obtained.

3. Results and discussion 3.1. GC-MS analysis Figure 5 and Table 1 show the NPS found in the forensic cases analyzed (70 doses). Additionally, this same table also shows the retention time, the molecular mass and the characteristic mass fragments of each one. The following substances were identified: 25INBOMe imine MDMA, Ketamine, DOB, caffeine, 25I-NBOMe, and 25H-NBOMe alone and combined. In 49 of them a single component was found, identified as DOB; two samples of these 49 were found with two components: DOB in combination with caffeine

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and ketamine, used as adulterants in some cases. As for the remaining 21 doses, the

detected NPS correspond to 25I-NBOMe combined in the same blotter with MDMA, 25I-

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NBOMe imine, and/or 25H-NBOMe.

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It should be noted that blotters with a single component (blue bar) are composed of the DOB drug and this represents 67.1 % of the analyzed doses; blotters with two components (orange bar) have different combinations: DOB-Caffeine, DOB-Ketamine, representing 2.9

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% of the analyzed doses; MDMA-25I-NBOMe and MDMA-25I-NBOMe imine, 11.4 %; as for blotters with three components (gray bar), the substances detected were: MDMA-25I-

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NBOMe-25I-NBOme imine, representing 11.4 %; and for blotters with four components (yellow bar), these combinations were identified: MDMA-25H-NBOMe-25I-NBOMe-25INBOme imine, in which 5.7 % of each substance was found in the doses analyzed (See

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Figure 6).

It is also noted that marketed blotters with a single component are more common, representing 67 % of the 70 analyzed doses. Blotters consisting of two components represent 16 %. Blotters with three and four components account for 11 and 6 %,

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respectively. The same figure indicates that the marketed blotters in at least these two cities (Barranquilla and Bogota) are adulterated: not one drug but two and even three drugs are included in a single dose. This, therefore, exposes consumers to different unintended effects.

As for the detected drugs and that are combined in the blotters (see Figure 6), there are drugs that are normally sold in tablets such as MDMA and NPS, reported in Colombia [2]. The drug known as DOB had the highest frequency in the 70 doses analyzed (see Figure

7a). It should be noted that this is so far the first report on this drug made in the country. In addition, drugs from the NBOMe series were identified (see Figure 7b, 7c and 8).

According to the previous scheme (Figure 6), these blotters subject consumers to unintended sensations, as they may perceive hallucinatory, entactogenic, or stimulating

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effects after a single dose; this depends on the substituents in the aromatic ring or close to it [11,12]. Besides, they enhance the hallucinatory and stimulating effect, which increases

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health risks and can cause even death [9,13]. All these NPS effects, too, were described by Hondebrink & cols [14], even when they are being combined with other types of drugs. The above reflects the risk in the consumption of this modality of sale of NPS of which it is

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evident that a stimulating substance (MDMA) and a hallucinogen (25I-NBOMe) are being combined in a single dose where it would cause a high risk of overdose and important

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[15,16] is increasingly common.

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adverse effects because we are also considered to be in a society where drug consumption

Finally, the marketing of the NPS’s depends on several social factors: time of year, reason

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for the party, and substance of consumption at a certain point. In addition, the target population is frequent LSD consumers [2,18]; this evidences the ignorance about what they really consume.

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Conclusions

Drugs impregnated in the blotters were identified with the developed analytical methodology. The blotters marketed as LSD in two cities in Colombia correspond to substances known as DOB, MDMA, and 25I-NBOMe and were found mixed in a single dose. This increases the risk of adverse health effects due to the combination with different types of drugs such as depressants such as ethyl alcohol, hallucinating, stimulants, which

would cause damage to the central nervous system and even death due to its potentiating effect in some of them. This work evidences the finding of NPS mixtures in two Colombian cities and the first work in Barranquilla that informs the general society of the commercialization of DOB in blotters.

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Declarations of interest: none CREDIT AUTHOR STATEMENT

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Catrin Mendoza: Conceptualization, Methodology, Validation, Investigation, Writing – Original Draft. Diana Mariño: Investigation, Supervision, Writing – Review and Editing, Visualization. Nancy Patiño: Supervision. Fabián López: Writing – Review and Editing. Álvaro Sarmiento: Data curation, Software, Validation. Daniel Trespalacios: Methodology, Validation.

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Acknowledgements

Thanks to the Laboratorio de Química of the Fiscalía General de la Nación and to the

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Laboratorio de Estupefacientes of the Instituto Nacional de Medicina Legal y Ciencias

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Forenses of Colombia for the drug samples provided for this investigation.

References [1]

Observatorio de Drogas de Colombia, Sustancias Psicoactivas, (n.d.). http://www.odc.gov.co/problematica-drogas/consumo-drogas/sustanciaspsicoactivas. Observatorio de Drogas de Colombia, Aparición de Nuevas Sustancias Psicoactivas

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en Colombia, 2017.

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http://www.odc.gov.co/Portals/1/publicaciones/pdf/consumo/sat/sat092017_boletin_ nuevas_sustancias_septiembre_2017.pdf.

UNODC, Informe mundial sobre las drogas 2018, UNODC Res. (2018) 1–10.

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[3]

http://fileserver.idpc.net/library/WDR18_ExSum_Spanish.pdf. I. Ezquiaga, M. Grifell, L. Galindo, L. Martínez, Á. Palma, P. Quintana, M. Ventura,

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E. Ribera, L. Pujol, I. Fornís, M. Torrens, M. Farré, Free communications Addictive

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behaviours, Elsevier Masson SAS, 2016. doi:10.1016/j.eurpsy.2016.01.006. Observatorio de Drogas de Colombia, Acciones y Resultados 2011 - 2013, 2013.

[6]

SWGDRUG, Recommendations, 2016.

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[5]

http://www.swgdrug.org/Documents/SWGDRUG Recommendations Version 71.pdf. [7]

G. Sánchez Robayo, Diego; Garzón Méndez, William; Taborda Ocampo, M. Rosero Moreano, Analysis of Blotter Papers Employed in the Commercialization of New

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Hallucinogenic Substances of the 2,5-Dimethoxy-, J. Braz. Chem. Soc. 27 (2016) 992–997. doi:http://dx.doi.org/10.5935/0103-5053.20150353.

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Z. Xiaoyu, Z. Yanbiao, Y. Hongxian, G. Lisheng, Z. Hui, Forensic Biomechanics Seized Blotters Containing One Regioisomer of 25I-NBOMe, J. Forensic Biomech. 9 (2018) 9–11. doi:10.4172/2090-2697.1000138.

[9]

D.J. Mariño-Gaviria, Detección post mortem de una nueva sustancia psicoactiva

DOC en humor vitreo, Colomb. Forense. 4 (2017). doi:https://doi.org/10.16925/cf.v4i1.1956. [10] D. Zuba, K. Sekuła, A. Buczek, 25C-NBOMe – New potent hallucinogenic substance identified on the drug market §, Forensic Sci. Int. 227 (2013) 7–14. doi:10.1016/j.forsciint.2012.08.027. [11] A.L. Thigpen, Chromatographic and mass spectral studies on mass equivalent substituted phenethylamines related to MDEA, MDMMA and MBDB, Auburn

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University, 2006.

http://etd.auburn.edu/bitstream/handle/10415/535/THIGPEN_ASHLEY_11.pdf?seq

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uence=1&isAllowed=y.

[12] D. Sánchez Robayo, Determinación de drogas de abuso de tipo sintético de la serie

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NBOMe, presentes en estampillas de papel y comercializadas en la ciudad de Bogotá, por cromatografía de gases acoplada a espectrometría de masas de trampa

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iónica (GC/MS IT) y detector de ioniz, Universidad de Caldas, 2016. [13] L. Morini, M. Bernini, S. Vezzoli, M. Restori, M. Moretti, S. Crenna, P. Papa, C.

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Locatelli, A. Marco, M. Osculati, C. Vignali, A. Groppi, Death after 25C-NBOMe and 25H-NBOMe consumption, Forensic Sci. Int. 279 (2017) e1–e6.

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doi:10.1016/j.forsciint.2017.08.028.

[14] L. Hondebrink, A. Zwartsen, R.H.S. Westerink, Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?, Pharmacol. Ther. (2017). doi:10.1016/j.pharmthera.2017.10.022.

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[15] A.F. Estrada, Guía para el Manejo de Emergencias Toxicológicas, 2018. [16] H. Cartago, E l policonsumo de las drogas ilícitas en los adolescentes de Hogares Crea de Barba de Polydrug use of illicit drugs among adolescen ts in Hogar Crea of Barba de Heredia and, (2013).

[17] C. Chemical, 25I-NBOMe imine analog, (2018). https://www.caymanchem.com/product/11968. [18] U. Nations, World Drug Report, New York, 2013.

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https://www.unodc.org/unodc/secured/wdr/wdr2013/World_Drug_Report_2013.pdf.

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Figure 1: Chemical structure of phenylethylamine.

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Figure 2: Blotters impregnated with NPS.

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Figure 3: Coding of the studied blotters.

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Figure 4: NPS used in the study at a 10 µg/mL concentration.

Distribution of the combinations of drugs identified in the blotters 5.7

1.4 11.4 25I-NBOMe Imine

5.7

28.5 %

1.4

1.4 %

Ketamine

67.1

2.9

70 %

1.4

Caffeine

10.0

11.4

1.4 %

5.7

25I-NBOMe

27.1 %

25H-NBOMe

5.7 0.0

5.7 % 10.0

20.0

30.0

40.0

Percentage Two components

50.0

60.0

70.0

Three components

Four components

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One component

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DOB

11.4

11.4

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Identified drugs

MDMA

18.5 %

DOB Caffeine

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DOB Ketamine

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Figure 5: Combinations of drugs identified in real cases.

MDMA 25I-NBOMe

MDMA

25I-NBOMe 25I-NBOMe imine

Figure 6: Scheme of components identified per blotter

MDMA 25I-NBOMe Imine

DOB 25I-NBOMe Imine 25H-NBOMe 25I-NBOMe

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Figure 7: (Left) Chromatogram of sample 54, 19 and 16, detection of DOB, 25I-NBOMe and 25H-NBOMe,

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SWGDRUG library.

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respectively. (Right) Comparison of mass spectra of (a) M54 sample; (b) M19 sample and (c) M16 and

Figure 8: Chemical structure of 25I-NBOMe imine (one of the identified drugs) of the NBOMe series [17].

Table 1. Retention time and fragment characteristics of the NPS found in the blotters samples. Molecular weight

NPS

(g/mol)

Time retention (min)

Characteristic fragment (m/z)

274.15

6.53

230, 105, 91,77, 44

MDMA

193.25

3.98

134, 106, 77, 58, 42

25I-NBOMe

427.28

16.64

394, 290, 278, 247, 150, 121, 91, 77, 65, 51, 39

25I-NBOMe imine

425.30

16.59

394, 148, 121, 105, 91, 77, 65, 51, 42, 39

25H-NBOMe

301.40

14.01

270, 150, 121, 91, 77, 65, 51, 39

Caffeine

194.19

6.59

194, 109, 82, 67, 44

Ketamine

237.72

7.06

209, 180, 138, 102, 75

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DOB