RESUMO
The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Alucinógenos , Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Brasil , N-Metil-3,4-Metilenodioxianfetamina/análise , Humanos , Drogas Ilícitas/química , Drogas Ilícitas/análise , Alucinógenos/análise , Alucinógenos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Contaminação de Medicamentos , Tráfico de DrogasRESUMO
New Psychoactive Substances (NPSs) are defined as a group of substances produced from molecular modifications of traditional drugs. These molecules represent a public health problem since information about their metabolites and toxicity is poorly understood. N-ethyl pentedrone (NEP) is an NPS that was identified in the illicit market for the first time in the mid-2010s, with four intoxication cases later described in the literature. This study aims to evaluate the metabolic stability of NEP as well as to identify its metabolites using three liver microsomes models. To investigate metabolic stability, NEP was incubated with rat (RLM), mouse (MLM) and human (HLM) liver microsomes and its concentration over time evaluated by liquid chromatography-mass spectrometry. For metabolite identification, the same procedure was employed, but the samples were analyzed by liquid chromatography-high resolution mass spectrometry. Different metabolism profiles were observed depending on the model employed and kinetic parameters were determined. The in vitro NEP elimination half-lives (t1/2) were 12.1, 187 and 770 min for the rat, mouse and human models, respectively. Additionally, in vitro intrinsic clearances (Cl int, in vitro) were 229 for rat, 14.8 for mouse, and 3.6 µL/min/mg in the human model, and in vivo intrinsic clearances (Cl int, in vivo) 128, 58.3, and 3.7 mL/min/kg, respectively. The HLM model had the lowest rate of metabolism when compared to RLM and MLM. Also, twelve NEP metabolites were identified from all models, but at different rates of production.
RESUMO
3',4'-Methylenedioxy-N-tert-butylcathinone (MDPT), also known as tBuONE or D-Tertylone, is a synthetic cathinone (SC) frequently abused for recreational purposes due to its potent stimulant effects and similarity to illegal substances like methamphetamine and ecstasy. The structural diversity and rapid introduction of new SC analogs to the market poses significant challenges for law enforcement and analytical methods for preliminary screening of illicit drugs. In this work, we present, for the first time, the electrochemical detection of MDPT using screen-printed electrodes modified with carbon nanofibers (SPE-CNF). MDPT exhibited three electrochemical processes (two oxidations and one reduction) on SPE-CNF. The proposed method for MDPT detection was optimized in 0.2 mol L-1 Britton-Robinson buffer solution at pH 10.0 using differential pulse voltammetry (DPV). The SPE-CNF showed a high stability for electrochemical responses of all redox processes of MDPT using the same or different electrodes, with relative standard deviations less than 4.7% and 1.5% (N = 3) for peak currents and peak potentials, respectively. Moreover, the proposed method provided a wide linear range for MDPT determination (0.90-112 µmol L-1) with low LOD (0.26 µmol L-1). Interference studies for two common adulterants, caffeine and paracetamol, and ten other illicit drugs, including amphetamine-like compounds and different SCs, showed that the proposed sensor is highly selective for the preliminarily identification of MDPT in seized forensic samples. Therefore, SPE-CNF with DPV can be successfully applied as a fast and simple screening method for MDPT identification in forensic analysis, addressing the significant challenges posed by the structural diversity of SCs.
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No início dos anos 2000, as Novas Substâncias Psicoativas (NPS) emergiram de forma sem precedentes causando uma drástica mudança no mercado de drogas sintéticas mundial. Estas substâncias são sintetizadas para fins ilícitos e mimetizam o efeito psicoativo das drogas tradicionais. Até o momento, mais de 1000 substâncias foram reportadas mundialmente, representando um grande problema de saúde pública principalmente associado ao desconhecimento das suas propriedades toxicológicas. Por este motivo, métodos analíticos para detectar e quantificar estas substâncias em materiais biológicos são importantes nos casos de toxicologia analítica e forense. Contudo, a tendência de reduzir o impacto ambiental destas metodologias tem ganhado popularidade com a Toxicologia Analítica Verde (GAT). Portanto, o objetivo do presente trabalho foi desenvolver novas técnicas analíticas para analisar as principais classes de NPS em amostras biológicas enquanto aplicando os princípios sustentáveis estabelecidos pela GAT. Os resultados obtidos no presente trabalho são apresentados como coletânea de artigos científicos publicados em revistas. Estes estão descritos nos capítulos 4 a 8. No capítulo 4, uma revisão sobre os desafios no desenvolvimento de técnicas de preparo de amostra para fins forenses é abordada com foco no uso das matrizes secas. No Capítulo 5, está descrito a aplicação da microextração líquido-líquido dispersiva para catinonas sintéticas em amostras de sangue total e urina. No capítulo 6, o artigo descreve o desenvolvimento da técnica microextração líquido-líquido homogênea com solventes de hidrofilicidade comutável para canabinoides sintéticos em amostras de plasma. No capítulo 7, a microextração em fase líquida em placas de 96 poços, cunhada extração paralela em membranas artificiais líquidas, foi desenvolvida para diferentes classes de drogas de abuso, incluindo NPS. O capítulo 8 mostra o desenvolvimento de uma extração por eletromembrana também no formato de placa de 96 poços para catinonas sintéticas em amostras de sangue total. Em todos os trabalhos, as técnicas de extração foram desenvolvidas, otimizadas e validadas. Os princípios da GAT foram aplicados de diferentes formas, como reduzindo o volume de amostra, simplificando os procedimentos, evitando o uso de solventes orgânicos, dentre outros. Assim, alternativas mais sustentáveis para a análise de drogas de abuso em amostras biológicas foram apresentadas e estas ajudam a consolidar e difundir o conceito do desenvolvimento de métodos analíticos com consciência ambiental além de fornecer ferramentas para auxiliar o controle das NPS no país
In the early 2000s, New Psychoactive Substances (NPS) emerged and unprecedentedly changed the illicit drug market. These substances are synthesized for illicit purposes and mimic the psychoactive effect of traditional drugs of abuse. To date, more than 1000 substances have been reported worldwide, representing a major public health problem mainly associated with their mostly unknown toxicological properties. In this context, analytical methods able to detect and quantitate these new drugs in biological specimens are important in cases of analytical and forensic toxicology. However, reducing the environmental impact of these methodologies has recently gained popularity with Green Analytical Toxicology (GAT). Therefore, the aim of this work was to develop new analytical techniques to analyze the main classes of NPS in biological samples while applying the environmentally friendly principles established by GAT. The results obtained throughout the development of the present work were split into four papers (chapters 4-8). In chapter 4, a review of common challenges faced during the development of new sample preparation techniques for forensic applications is described focusing on the use of dried matrices. In chapter 5, the application of dispersive liquid-liquid microextraction for synthetic cathinones in whole blood and urine samples is described. In chapter 6, the application of the somewhat recent switchable hydrophilicity solvent-based homogenous liquidliquid microextraction to synthetic cannabinoids in plasma samples is reported. In chapter 7, liquid-phase microextraction in the 96-well plate format, termed parallel artificial liquid membrane extraction, for different classes of drugs of abuse, including NPS, in plasma samples is presented. In chapter 8, an electromembrane extraction in the 96-well plate format for synthetic cathinones in whole blood samples was developed. In this work, sample preparation techniques were developed, optimized and validated. The principles of sustainable chemistry in method development were applied in different ways, such as reducing the sample volume, simplifying procedures, avoiding the use of organic solvents, among others. Thus, greener alternatives were presented for the analysis of drugs of abuse in biological samples and contribute to consolidate and spread this trend of environmental consciousness during method development. Additionally, valuable techniques that can be used in the combat against NPS were provided
Assuntos
Psicotrópicos/efeitos adversos , Drogas Ilícitas/efeitos adversos , Toxicologia Forense/métodos , Espectrometria de Massa com Cromatografia Líquida/métodos , Canabinoides/farmacologia , Preparações Farmacêuticas/análise , Catinona Sintética/farmacologiaRESUMO
La cantidad de nuevas sustancias psicoactivas (NSP) aumenta en el mercado global cada año. El uso de tecnologías para la producción y la comercialización de las sustancias sintéticas y una demanda exigente de efectos psicotrópicos más potentes son algunos de los factores que contribuyen al incremento de una oferta más variada, así como a la cantidad de consumidores de algún tipo de droga. El desarrollo de herramientas analíticas fiables con capacidad de respuesta in situ para una evaluación preliminar contribuye, significativamente, con la generación de información para atender casos de intoxicaciones, aplicar correctamente la legislación de los países e, inclusive, aportar datos reales para una reclasificación más objetiva de las drogas basada en criterios científicos. Los sensores electroquímicos han ganado terreno en áreas de las ciencias forenses como la toxicología. El uso de tecnologías especializadas para crear electrodos miniaturizados con modificaciones, principalmente con materiales nanoestructurados, guía el desarrollo de dispositivos portátiles de fácil manipulación, altamente versátiles y que requieren micro-cantidades de la muestra. Asimismo, algunos sensores electroquímicos presentan parámetros de desempeño -como límites de detección (LOD) de hasta 0,608 pg/mL, sensibilidad y precisión- que son analíticamente comparables, bajo ciertas condiciones, con las metodologías convencionales acopladas con la espectrometría de masas, las cuales muestran LOD del orden de magnitud entre 10-9 g/mL y 10-12 g/mL para la determinación de algunas drogas. Esta revisión se enfoca en la aplicación y comparación analítica de los sensores electroquímicos voltamperométricos para la determinación de bencilpiperazina (BZP), meta-clorofenilpiperazina (mCPP), 25B-NBO-Me, dimetiltriptamina (DMT), mefedrona (4-MMC), 4-metiletcatinona (4-MEC) y fentanilo (FYL) en representación de las drogas emergentes que se pueden conseguir actualmente en el mercado de las sustancias psicoactivas.
The number of new psychoactive substances (NPS) is increasing on the drug global market every year. New technologies for the production and marketing of synthetic substances, along with a rigorous demand for more powerful psychotropic effects, are some of the factors that contribute to the increase in a more varied supply, as well as the number of drug users. The development of reliable analytical tools with an on-site response capacity for a preliminary determination contributes significantly to the generation of data for the proper care of situations such as poisoning, the correct application of the country's legislation, and even the provision of objective criteria for the reclassification of the substances. Electrochemical sensors have gained ground in areas of forensic science. The use of specialized technologies to manufacture miniaturized electrodes based on modifications, mainly with nanostructured materials, guides the development of versatile easy-to-handle portable devices that require microquantities of the sample. Likewise, some electrochemical sensors have performance parameters such as detection limits (LOD) up to 0.608 pg/mL, sensitivity and precision that are analytically comparable, under certain conditions, with conventional methodologies coupled with mass detection, which show LOD of the order of magnitude between 10-9 g/mL and 10-12 g/mL for drug determination. This review focuses on the application and comparison of voltammetric electrochemical sensors for the determination of benzylpiperazine (BZP), meta-chlorophenylpiperazine (mCPP), 25B-NBO-Me, dimethyltryptamine (DMT), mephedrone (4-MMC), 4-methylethcathinone (4-MEC) and fentanyl (FYL) representing the emerging drugs available to date on the psychoactive substances market.
A quantidade de novas substâncias psicoativas (NSP) sintéticas aumenta a cada ano no mercado global. A utilização de novas tecnologias de produção e comercialização de substâncias, combinado com uma demanda exigente de efeitos psicotrópicos mais potentes, são alguns dos fatores que contribuem para o aumento de uma oferta mais ampla, assim como a quantidade dos números de consumidores de algum tipo de droga. O desenvolvimento de ferramentas analíticas confiáveis e com uma capacidade de resposta in situ para uma avaliação preliminar, contribuem significativamente para a geração de informações científicas para cuidar casos de envenenamento, aplicar corretamente a lei, e até fornecer dados reais para uma reclassificação mais objetiva de drogas com base em critérios científicos. Sensores eletroquímicos ganharam espaço em áreas da ciência forense. A utilização de tecnologias especializadas para criação de eletrodos miniaturizados com modificações, principalmente com materiais nanoestruturados, norteiam o desenvolvimento de dispositivos portáteis altamente versáteis, de fácil manuseio e que necessitam de microquantidades da amostra. Da mesma forma, alguns sensores eletroquímicos apresentam parâmetros de desempenho -como limites de detecção (LOD) até 0.608 pg/mL, sensibilidade e precisão- que são analiticamente comparáveis, sob certas condições, com metodologias convencionais com detecção de massa -mostram LOD de a ordem de grandeza entre 10-9g/mL e 10-12g/mL para a determinação de determinados medicamentos-. Esta revisão tem como foco a aplicação e comparação analítica de sensores eletro-químicos voltamétricos para determinação de benzilpiperazina (BZP), meta-clorofenilpiperazina (mCPP), 25B-NBOMe, dimetiltriptamina (DMT), mefedrona (4-MMC), 4-metilethcatinona (4-MEC) e fentanilo (FYL), que representam os drogas emergentes disponíveis até o momento no mercado de substâncias psicoativas.
RESUMO
The actual illicit market for synthetic drugs is characterized by a wide variety of psychoactive substances of different chemical and pharmacological classes, such as amphetamine-type stimulants and new psychoactive substances. The knowledge about its chemical composition, as well as the nature and quantity of the active substances present, is important for emergency care in intoxication cases by these substances and to establish adequate chemical and toxicological analysis procedures in forensic laboratories. The aim of this work was to study the prevalence of amphetamine-type stimulants and new psychoactive substances in the states of Bahia and Sergipe, in the northeast region of Brazil, involving samples of drugs seized by the local police forces from 2014 to 2019. In a total of 121 seized and analyzed samples, in which ecstasy tablets predominated (n = 101), nineteen substances were identified using GC-MS and 1D NMR techniques, comprising classical synthetic drugs and new psychoactive substances (NPS). In order to determine the composition of ecstasy tablets, an analytical method based on GC-MS was applied after validation. Analyzes of 101 ecstasy tablets showed that MDMA was the main substance, being found in 57% of the samples, in amounts between 27.3 and 187.1 mg per tablet. In addition, mixtures of MDMA, MDA, synthetic cathinones and caffeine were observed in 34 samples. These results demonstrate that the variety of substances found and the composition of seized materials in northeast Brazil is similar to other studies carried out previously in other Brazilian regions.
Assuntos
Estimulantes do Sistema Nervoso Central , Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Medicamentos Sintéticos , N-Metil-3,4-Metilenodioxianfetamina/análise , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Drogas Ilícitas/análise , Estimulantes do Sistema Nervoso Central/análise , Anfetamina/análise , Comprimidos , Psicotrópicos/análiseRESUMO
PURPOSE: MDA-19 or BZO-HEXOXIZID (N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-benzohydrazide), in a more recent nomenclature, was first synthesized in 2008 as a selective type-2 cannabinoid receptor (CB2) agonist due to its potential to treat neuropathic pain. In Brazil, this substance was identified in a series of 53 apprehensions between September 2021 and February 2022. Nevertheless, what intrigues toxicologists is that BZO-HEXOXIZID does not exert significant type-1 cannabinoid receptor (CB1) agonism-which is responsible for the well-known psychoactivity of Δ-9-tetrahydrocannabinol. Thus, the objective of this work is to report the first apprehension and identification of BZO-HEXOXIZID in Brazil and to discuss pharmacologically the possible reasons why a CB2 agonist has been incorporated to the illicit market. METHODS: Suspected seized samples were sent to the Laboratory of the Scientific Police of the State of Sao Paulo. After the screening, samples were confirmed for the presence of BZO-HEXOXIZID using chromatography gas-mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance techniques. RESULTS: Of the 53 samples analyzed, 25 contained only BZO-HEXOXIZID and 28 with mixtures, of which 11 with the CB1 agonist ADB-BUTINACA. Other substances were found in association such as cocaine and caffeine. CONCLUSIONS: BZO-HEXOXIZID was detected in a series of seized materials for the first time in Brazil. Nevertheless, there are still unanswered questions regarding the use of this selective CB2 agonist as a drug of abuse.
Assuntos
Agonistas de Receptores de Canabinoides , Neuralgia , Humanos , Agonistas de Receptores de Canabinoides/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Brasil , Receptores de CanabinoidesRESUMO
PURPOSE: New psychoactive substances (NPS) are not controlled under the Single Convention on Narcotic Drugs of 1961 or the 1971 Convention, but they may pose a public health threat. Knowledge of the main properties and toxicological effects of these substances is lacking. According to the current Drugs Law (Law n. 11.343/2006), the Brazilian Surveillance Agency issues directives for forbidden substances in Brazil, and structural classes of synthetic cannabinoids, cathinones, and phenylethylamines are considered illicit drugs. Considering that data on these controlled substances are scattered, the main objective of this work was to collect and organize data to generate relevant information on the toxicological properties of NPS. METHODS: We carried out a literature review collecting information on the acute, chronic, and post-mortem toxicity of these classes of NSP. We searched info in five scientific databases considering works from 2017 to 2021 and performed a statistical evaluation of the data. RESULTS: Results have shown a general lack of studies in this field given that many NPS have not had their toxicity evaluated. We observed a significant difference in the volume of data concerning acute and chronic/post-mortem toxicity. Moreover, studies on the adverse effects of polydrug use are scarce. CONCLUSIONS: More in-depth information about the main threats involving NPS use are needed.
Assuntos
Canabinoides , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Psicotrópicos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Drogas Ilícitas/toxicidade , Canabinoides/toxicidade , Substâncias ControladasRESUMO
PURPOSE: Synthetic cannabinoid receptor agonists (SCRAs) are a class of varied compounds that mimic the effects of natural cannabinoids found in cannabis. Because they have a wide range of diverse structures, they vary widely in their potency. The abuse of new psychoactive substances (NPS) in prisons was reported in many European countries and in the USA. In the present study, we have described the identification of SCRAs in 56 infused paper sheet samples, seized mainly in Brazilian prisons between 2016 and 2020. METHODS: The materials were seized by local or federal law enforcement and analyzed by São Paulo State Police or Brazilian Federal Police using gas chromatography-mass spectrometry, attenuated total reflection-Fourier transform infrared spectroscopy, liquid chromatography-high-resolution mass spectrometry or nuclear magnetic resonance spectrometry. RESULTS: Most of these samples (87.5%) were seized in 2019-2020; seven different SCRAs were identified in samples, and the most frequently identified substances were MDMB-4en-PINACA (23.6%) and 5F-MDMB-PICA (36.4%), the newest SCRAs emerging recently. CONCLUSIONS: As observed in Europe and the USA, Brazil also shows the prevalence of indazole-3-carboxamides and indole-3-carboxamides among SCRAs seizures in the prison system. This phenomenon is spreading all over the world at this moment. These data on the prevalence could help to alert judicial authorities to shutting down the introduction of NPS, including SCRAs, into prisons to ensure safety and security for avoiding health risks of prisoners and staff, leading to positive effects in this population. To our knowledge, this is the first demonstration of SCRAs smuggling into prisons in Latin America.
Assuntos
Agonistas de Receptores de Canabinoides , Prisioneiros , Humanos , Prisões , Brasil/epidemiologiaRESUMO
PURPOSE: This study aimed to validate a modified QuEChERS method followed by ultra-high performance liquid chromatography-tandem mass spectrometry to determine 79 new psychoactive substances (NPS) and other drugs in blood and urine. METHODS: Prescription drugs (n = 23), synthetic cathinones (n = 13), phenethylamines (n = 11); synthetic cannabinoids (n = 8), amphetamines (n = 7) and other psychoactive substances (n = 17) were included in the method. 500 µL of biological fluid was extracted with 2 mL of water/ACN (1:1), 500 mg of anhydrous MgSO4/NaOAc (4:1) added, followed by a supernatant cleanup with 25 mg of primary secondary amine and 75 mg of anhydrous MgSO4. Quantification was done using matrix-matched calibration curves and deuterated internal standards. RESULTS: The method was satisfactorily validated for blood and urine at limit of quantifications ranging from 0.4 to 16 ng/mL, and applied to the analysis of 54 blood (38 postmortem and 16 antemortem) and 16 antemortem urine samples from 68 forensic cases. All urine samples and 59.3% of the blood samples were positive for at least one analyte. Twenty-two analytes were detected in at least one biological sample, including the synthetic cathinones ethylone (222 ng/mL, antemortem blood), eutylone (246 and 446 ng/mL, urine), and N-ethylpentylone (597 and 7.3 ng/mL, postmortem and antemortem blood, respectively). CONCLUSIONS: The validated method was shown to be suitable for the analysis of blood and urine forensic samples and an important tool to collect information on emerging drug threats and understanding the impact of NPS and other drugs in poisoning cases.
Assuntos
Líquidos Corporais , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Medicina Legal , Fármacos do Sistema Nervoso Central , FenetilaminasRESUMO
New psychoactive substances (NPS) are an emerging public health issue and deaths are commonly associated with polydrug abuse. Moreover, the number of new substances available is constantly increasing, causing intoxications in low doses, characteristics that impose to toxicology and forensic laboratories to keep routine methods up to date, with high detectability and constantly acquiring new analytical standards. Likewise, NPS metabolites and respective elimination pathways are usually unknown, making it difficult the detection and confirmation of the drug involved in the fatal case in an analytical routine. A literature search was performed on PubMed, Scopus and Web of Science databases for papers related to chromatographic analyses from fatal cases related to NPS use published from 2016 to 2021. A total of 96 papers were retrieved and reviewed in this study. Opioids, synthetic cathinones, phenethylamines/amphetamines and cannabinoids were the NPS classes most found in the fatal cases. In many cases, multiple compounds were detected in the biological samples, including prescription and other illegal drugs. Liquid chromatography-tandem mass spectrometry, an alternative to overcome the gas chromatography-mass spectrometry limitations for some compounds, was the analytical technique most used in the studies, and high resolution mass spectrometry was often applied to NPS metabolite investigation and structural characterization and identification of unknown compounds. Toxicological screening and quantitation methods need to be continuously updated to include new substances that are emerging on the drug market that can be fatal at very low doses.
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Lucy in the Sky with Diamonds, a John Lennon song that was a hit in the 1960s, was born amidst a social context enlightened by lysergic acid diethylamide (LSD). In Brazil, both the drug and the song were very popular at the time, although it gradually mitigated. Nevertheless, while the song remains out of the spotlight, LSD derivatives are currently gaining attention with the rising of the new psychoactive substances (NPS). With this new presentation, the drug is returning to Brazil after a few decades and herein we report and discuss the first cases of an LSD prodrug seized in our country. Nine suspected blotter paper samples were seized by the Sao Paulo State Police in different cities of the State. Gas chromatography-mass spectrometry (GC-MS), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and liquid chromatography coupled with electrospray ionization-mass spectrometry (LC-ESI-MS) analyses were utilized to confirm the identity of the LSD derivative. The compound was identified as 4-acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52 or 1A-LSD) and no other active substance was detected in all samples. The identity of the unknown compound found in seized blotter papers has been successfully confirmed as an LSD prodrug, ALD-52, which was not controlled by Brazilian legislation. The arrival of a new type of designer drug in Brazil is in support by other reports, although those are still scarce and should not be overlooked. Altogether, these findings indicate the rising of a new NPS strategy that merits proper discussion.
Assuntos
Dietilamida do Ácido Lisérgico , Pró-Fármacos , Brasil , Cromatografia Líquida/métodos , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
The use of drugs of abuse has grown significantly in recent decades. In forensic chemistry, methods of identifying and characterizing illicit drugs contribute to the interests of researchers, experts, and public security authorities. Among existing methods, portable Raman spectroscopy is notable for performing rapid, non-destructive, and highly selective analysis in the laboratory or on-site. When the resulting spectral data are paired with chemometric tools, methods of exploratory analysis and multivariate calibration can be developed. Thus, this work describes the application of Raman spectroscopy associated with principal component analysis (PCA) and interval principal component analysis (iPCA) to assessing trends in samples of cocaine (n = 40), crack (n = 33), and their main adulterants (n = 5) and diluents (n = 5), tablets of ecstasy (n = 14), designer drugs papers (n = 27), and alcoholic solutions adulterated with benzodiazepines (alprazolam and diazepam). In addition, competitive adaptive reweighted sampling (CARS) combined with partial least squares (PLS) regression (CARSPLS) was used to quantify adulterants (benzocaine, lidocaine, and procaine) in binary mixtures with crack (n = 21) and solutions of cachaça adulterated with bromazepam (n = 11).
Assuntos
Drogas Ilícitas , Análise Espectral Raman , Drogas Ilícitas/análise , Análise dos Mínimos Quadrados , Análise de Componente Principal , Análise Espectral Raman/métodos , ComprimidosRESUMO
Dried matrix spots (DMS) has gained the attention of different professionals in different fields, including toxicology. Investigations have been carried out in order to assess the potential of using DMS for the analysis of illicit substances, the main interest of forensic toxicologists. This technique uses minimal volumes of samples and solvents, resulting in simple and rapid extraction procedures. Furthermore, it has proved to increase analyte stability, improving storage and transportation. However, DMS presents some limitations: the hematocrit influencing accuracy and inconsistencies regarding the means of spotting samples and adding internal standard on paper. Thus, we provide an overview of analytical methodologies with forensic applications focusing on drugs of abuse and discussing the main particularities, limitations and achievements.
RESUMO
BACKGROUND: New psychoactive substances (NPS) use is a worldwide public health issue. Knowing the prevalence of NPS guides public health and legal policies to address the problem. The objective of this study was to identify NPS in Brazil through the analysis of oral fluid (OF) samples collected at parties and electronic music festivals. METHODS: Anonymous questionnaires and oral fluid samples were collected from volunteers (≥18 years) who reported the consumption of at least one illicit psychoactive substance in the last 24 h. Oral fluid sample collections occurred at eleven parties and two electronic music festivals over 16 months (2018-2020). Questionnaire answers were matched to oral fluid toxicological results. RESULTS: Of 462 oral fluid samples, 39.2 % were positive for at least one NPS by liquid chromatographyâtandem mass spectrometry (LC-MS/MS). The most prevalent NPS was ketamine (29.4 %), followed by methylone (6.1 %) and N-ethylpentylone (4.1 %); however, MDMA was the most commonly identified (88.5 %) illicit psychoactive substance. More than one drug was identified in 79.9 % of samples, with two (34.2 %) and three (23.4 %) substances most commonly observed. Only 5 % of volunteers reported recent NPS consumption. CONCLUSION: MDMA is still the most common party and electronic music festival drug, although NPS were identified in more than one-third of oral fluid samples.
Assuntos
Drogas Ilícitas , Música , Transtornos Relacionados ao Uso de Substâncias , Brasil/epidemiologia , Cromatografia Líquida , Eletrônica , Férias e Feriados , Humanos , Prevalência , Psicotrópicos , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Espectrometria de Massas em TandemRESUMO
The consumption of design drugs, frequently known as new psychoactive substances (NPS), has increased considerably worldwide, becoming a severe issue for the responsible governmental agencies. These illicit substances can be defined as synthetic compounds produced in clandestine laboratories in order to act as analogs of schedule drugs mimetizing its chemical structure and improving its pharmacological effects while hampering the control and making regulation more complicated. In this way, the development of new methodologies for chemical analysis of NPS drugs is indispensable to determine a novel class of drugs arising from the underground market. Therefore, this work shows the use of high-resolution mass spectrometry Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) applying different ionization sources such as paper spray ionization (PSI) and electrospray ionization (ESI) in the evaluation of miscellaneous of seized drugs samples as blotter paper (n = 79) and tablet (n = 100). Also, an elucidative analysis was performed by ESI(+)MS/MS experiments, and fragmentation mechanisms were proposed to confirm the chemical structure of compounds identified. Besides, the results of ESI(+) and PSI(+)-FT-ICR MS were compared with those of GC-MS, revealing that ESI(+)MS showed greater detection efficiency among the methodologies employed in this study. Moreover, this study stands out as a guide for the chemical analysis of NPS drugs, highlighting the differences between the techniques of ESI(+)-FT-ICR MS, PSI(+)-FT-ICR MS, and GC-MS.
Assuntos
Drogas Desenhadas/química , Drogas Ilícitas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Gasosa-Espectrometria de Massas , Papel , Espectrometria de Massas em TandemRESUMO
NBOMe and NBOH are new psychoactive substances with potent activity on serotonin 5-HT2a receptors causing serious toxic effects, including serotonin toxidrome and death. The aim of this work was to develop a comprehensive MS/MS protocol, using triple quadrupole mass spectrometers coupled to LC and GC, for rapid screening and quantitation of NBOMes and NBOHs in seized blotter papers. Different scan methods (neutral loss, precursor ion or multiple reaction monitoring) were used to obtain structural information of phenylethylamine class. The developed protocol was validated for qualitative and quantitative analysis, showing a satisfactory limit of detection (1 ng/mL), with excellent selectivity, imprecision (intra and interday imprecision lower than 1.2 % RSD) and accuracy (between -7.1 and +5.6 %, n = 15), as well as bias values. The analysis of real samples shown that NBOH compounds were the most frequently detected, with concentrations ranging from 0.1 to 1,929 µg per blotter sample. Triple quadrupole mass spectrometers can be a useful tool for identification of new psychoactive substances. A comprehensive protocol using both LC-MS/MS and GC-MS/MS, with different scanning modes, have been developed and showed to be useful to screening NBOMe and NBOH in blotter papers.
RESUMO
Designer drugs or new psychoactive substances (NPS) are a heterogeneous group of substances obtained through the modification of chemical structure of some natural products or drugs. NPS illegally commercialized in blotter papers mimicking the most common form of LSD consumption, with a great variability of colours and symbols, have largely increased worldwide, including in Brazil, becoming an important emerging public health issue. In this study, we have evaluated the presence and profile of NPS in blotters seized in the State of Santa Catarina, Brazil, over the period of 2011 to 2017. The state government criminal forensics staff has performed gas chromatography-mass spectrometer (GC-MS) analyses in order to determine the chemical composition of the blotters. During the evaluated period, there was a considerable increase in the seizing of blotters events, from 87 in 2011, to 301 in 2016 and reaching 277 in 2017. There was also an increase in the number of blotters seized per event. Interestingly, while in 2011, 100% of blotters contained LSD, this number decreased to 0,1% in 2014, and achieved 17,6% in 2017, when up to 25 different substances were detected in blotters seized. Drugs such as DOx, NBOMe, fentanyl, mescaline derivatives, triptamines, cathinones, and synthetic cannabinoids were detected and became the major substances found in blotters. In some cases, more than one substance was found in the same blotter, characterizing a new mixture scenario. The presence of several new psychoactive substances in blotters is a reality in forensic toxicology. In Brazil, it might be related to the fact that most of these substances were not considered illegal by Brazilian legislation by the time they emerged.
Assuntos
Drogas Desenhadas/análise , Drogas Ilícitas/análise , Papel , Psicotrópicos/análise , Brasil/epidemiologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Dietilamida do Ácido Lisérgico/análise , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Synthetic cathinones continue to proliferate in clandestine drug markets worldwide. N-ethylnorpentylone (also known as N-ethylpentylone or ephylone) is a popular emergent cathinone, yet little information is available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, and pharmacological mechanism of action for N-ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify N-ethylnorpentylone in blood obtained from human cases. Clinical features exhibited by the intoxicated individuals are described. The activity of N-ethylnorpentylone at plasma membrane transporters for dopamine (DAT), norepinephrine (NET) and 5-HT (SERT) was assessed using in vitro assays measuring uptake inhibition and evoked release of [3 H] neurotransmitters in rat brain synaptosomes. Our LC-MS/MS method assayed N-ethylnorpentylone concentrations with limits of detection and quantification of 1 and 5 ng/mL, respectively. Quantitation was linear from 5 to 500 ng/mL, and the method displayed specificity and reproducibility. Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death. N-Ethylnorpentylone was a potent inhibitor at DAT (IC50 = 37 nM), NET (IC50 = 105 nM) and SERT (IC50 = 383 nM) but displayed no transporter releasing activity. We present a validated method for quantifying N-ethylnorpentylone in human case work. The drug is a psychomotor stimulant capable of inducing serious cardiovascular and neurological side-effects which can be fatal. In vitro findings indicate that N-ethylnorpentylone exerts its effects by potent blockade of DAT and NET, thereby elevating extracellular levels of dopamine and norepinephrine in the brain and periphery.
Assuntos
Benzodioxóis/sangue , Benzodioxóis/farmacologia , Butilaminas/sangue , Butilaminas/farmacologia , Adolescente , Adulto , Animais , Benzodioxóis/toxicidade , Butilaminas/toxicidade , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/toxicidade , Cromatografia Líquida , Inibidores da Captação de Dopamina/sangue , Inibidores da Captação de Dopamina/farmacologia , Feminino , Humanos , Limite de Detecção , Masculino , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Inibidores Seletivos de Recaptação de Serotonina/sangue , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sinaptossomos/metabolismo , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
Several new psychoactive substances (NPS) have reached the illegal drug market in recent years, and ecstasy-like tablets are one of the forms affected by this change. Cathinones and tryptamines have increasingly been found in ecstasy-like seized samples as well as other amphetamine type stimulants. A presumptive method for identifying different drugs in seized ecstasy tablets (n=92) using ATR-FTIR (attenuated total reflectance - Fourier transform infrared spectroscopy) and PLS-DA (partial least squares discriminant analysis) was developed. A hierarchical strategy of sequential modeling was performed with PLS-DA. The main model discriminated four classes: 5-MeO-MIPT, methylenedioxyamphetamines (MDMA and MDA), methamphetamine, and cathinones. Two submodels were built to identify drugs present in MDs and cathinones classes. Models were validated through the estimate of figures of merit. The average reliability rate (RLR) of the main model was 96.8% and accordance (ACC) was 100%. For the submodels, RLR and ACC were 100%. The reliability of the models was corroborated through their spectral interpretation. Thus, spectral assignments were performed by associating informative vectors of each specific modeled class to the respective drugs. The developed method is simple, fast, and can be applied to the forensic laboratory routine, leading to objective results reports useful for forensic scientists and law enforcement.