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1.
Forensic Sci Int ; 306: 110002, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31864775

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 , Papel , Psicotrópicos/análise , Brasil/epidemiologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Dietilamida do Ácido Lisérgico/análise , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
2.
Forensic Sci Int ; 307: 110101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865266

RESUMO

Flualprazolam is a novel designer benzodiazepine, structurally related to alprazolam, flubromazolam and triazolam. In the last couple of years, it has been frequently detected in seizures and in forensic cases in Sweden and Finland. However, there is a lack of published blood concentrations for the drug, which presents difficulties when assessing its relevance for the cause of death. A quantitative method for the determination of flualprazolam in post-mortem blood was developed and validated, and subsequently used to analyse samples from 33 deaths previously screened as testing positive for flualprazolam in Sweden and Finland. Most of the cases in the study were accidental deaths (61 %) or suicides (18 %). The median (range) flualprazolam concentration was 18.0 (3.0-68) ng/g. The majority of the deceased were male (82 %) and the median age was 30 years. The median age in the Swedish cases was significantly higher (35 years) than in the Finnish cases (23 years) (p< 0.05). Poly-drug use and particularly the concomitant use of flualprazolam and opioids were very common in the study population. Most of the cases that were positive for flualprazolam were fatal poisonings by a drug (N=23), and in 13 cases, flualprazolam was implicated in the cause of death. Combining the resources of two countries in which all post-mortem toxicology is centralised provided a more comprehensive insight into the toxicology of flualprazolam. Research on novel psychoactive substances, such as flualprazolam, is required in order to be able to provide scientific evidence on the risks of these new substances for drug administration and potential users.


Assuntos
Benzodiazepinas/sangue , Drogas Desenhadas/análise , Psicotrópicos/sangue , Triazolam/sangue , Acidentes/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Benzodiazepinas/envenenamento , Drogas Desenhadas/química , Drogas Desenhadas/envenenamento , Feminino , Finlândia/epidemiologia , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Psicotrópicos/química , Psicotrópicos/envenenamento , Distribuição por Sexo , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Suicídio/estatística & dados numéricos , Suécia/epidemiologia , Triazolam/envenenamento , Adulto Jovem
3.
Forensic Sci Int ; 304: 109972, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31604205

RESUMO

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) is a designer hallucinogen that is a synthetic tryptamine derivative. It is highly abused and is involved in criminal activities because of its psychotropic properties. Herein, we presented an UHPLC-MS/MS method allowing for the qualitative and quantitative determination of 5-MeO-DiPT in human hair. The hair was first decontaminated and then cut into pieces. Thirty milligrams of hair samples was pulverized below 4°C in the presence of 0.5mL deionized water containing 0.1% formic acid. After centrifuging twice, 5µL of supernatant was injected into the LC-MS/MS system. A T3 column (100mm×2.1mm, 1.8µm) was used, and mobile phases consisted of 20mmol/L ammonium acetate, 5% acetonitrile and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). The gradient elution was used at a flow rate of 0.3mL/min. The resulting calibration curve for 5-MeO-DiPT was y=281.50213x+0.00231 (R2=0.992), the limit of detection (LOD) was 0.05pg/mg, and the lower limit of quantification (LLOQ) was 0.1pg/mg. The accuracy was between 92.1% and 105.6%, and the intra- and interday precision, recovery and matrix effect were acceptable. The validated method was successfully used in 106 real cases, and the concentration of 5-MeO-DiPT in hair samples of these suspected users was 0.2-7532.5pg/mg. These cases present data to document illegal 5-MeO-DiPT use.


Assuntos
5-Metoxitriptamina/análogos & derivados , Drogas Desenhadas/análise , Cabelo/química , Alucinógenos/análise , Detecção do Abuso de Substâncias/métodos , 5-Metoxitriptamina/análise , 5-Metoxitriptamina/química , Adulto , Cromatografia Líquida de Alta Pressão , Drogas Desenhadas/química , Feminino , Toxicologia Forense , Alucinógenos/química , Humanos , Limite de Detecção , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estrutura Molecular , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto Jovem
4.
Forensic Sci Int ; 303: 109959, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31546164

RESUMO

The organ distribution of 3-fluorophenmetrazine (3-FPM), pyrazolam, diclazepam as well as its main metabolites delorazepam, lormetazepam and lorazepam, was investigated. A solid phase extraction (SPE) and a QuEChERS (acronym for quick, easy, cheap, effective, rugged and safe) - approach were used for the extraction of the analytes from human tissues, body fluids and stomach contents. The detection was performed on a liquid chromatography-tandem mass spectrometry system (LCMS/MS). The analytes of interest were detected in all body fluids and tissues. Results showed femoral blood concentrations of 10 µg/L for 3-FPM, 28 µg/L for pyrazolam, 1 µg/L for diclazepam, 100 µg/L for delorazepam, 6 µg/L for lormetazepam, and 22 µg/L for lorazepam. Tissues (muscle, kidney and liver) and bile exhibited higher concentrations of the mentioned analytes than in blood. Additional positive findings in femoral blood were for 2-fluoroamphetamine (2-FA, approx. 89 µg/L), 2-flourometamphetamine (2-FMA, hint), methiopropamine (approx. 2.2 µg/L), amphetamine (approx. 21 µg/L) and caffeine (positive). Delorazepam showed the highest ratio of heart (C) and femoral blood (P) concentration (C/P ratio = 2.5), supported by the concentrations detected in psoas muscle (430 µg/kg) and stomach content (approx. 210 µg/L, absolute 84 µg). The C/P ratio indicates that delorazepam displays susceptibility for post-mortem redistribution (PMR), supported by the findings in muscle tissue. 3-FPM, pyrazolam, diclazepam, lorazepam and lormetazepam did apparently not exhibit any PMR. The cause of death, in conjunction with autopsy findings was concluded as a positional asphyxia promoted by poly-drug intoxication by arising from designer benzodiazepines and the presence of synthetic stimulants.


Assuntos
Benzodiazepinas/farmacocinética , Drogas Desenhadas/farmacocinética , Diazepam/análogos & derivados , Fenmetrazina/análogos & derivados , Mudanças Depois da Morte , Adulto , Benzodiazepinas/análise , Bile/química , Líquidos Corporais/química , Química Encefálica , Drogas Desenhadas/análise , Diazepam/análise , Diazepam/farmacocinética , Toxicologia Forense , Conteúdo Gastrointestinal/química , Humanos , Rim/química , Fígado/química , Lorazepam/análogos & derivados , Lorazepam/análise , Lorazepam/farmacocinética , Pulmão/química , Masculino , Nordazepam/análogos & derivados , Nordazepam/análise , Nordazepam/farmacocinética , Líquido Pericárdico/química , Fenmetrazina/análise , Fenmetrazina/farmacocinética , Músculos Psoas/química , Espectrometria de Massas em Tandem
5.
Drug Test Anal ; 11(10): 1480-1485, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479592

RESUMO

The structural diversity of synthetic cannabinoids makes it a challenging task to have a comprehensive screening method for this class of drugs. The difficulty is increased by the fact that some synthetic cannabinoids undergo thermal decomposition during common routes of administration, such as smoking or vaping. CUMYL-PEGACLONE is a relatively new synthetic cannabinoid which has a structural variant from most other synthetic cannabinoids: a γ-carbolinone core. To investigate its thermal stability, CUMYL-PEGACLONE was heated in an oven at temperatures ranging from 200 to 350o C, and a major thermal degradation product, N-pentyl-γ-carbolinone, was subsequently identified. Unlike some other synthetic cannabinoids, the thermal degradation product of CUMYL-PEGACLONE is not one of its known metabolites, nor were any known metabolites detected during the thermal stability experiments. The degradation product was formed in significant amounts at temperatures above 250°C, and has been detected (along with CUMYL-PEGACLONE) in case samples, including post-mortem blood and urine, and residue found at a scene.


Assuntos
Agonistas de Receptores de Canabinoides/sangue , Agonistas de Receptores de Canabinoides/urina , Canabinoides/sangue , Canabinoides/urina , Detecção do Abuso de Substâncias/métodos , Autopsia , Drogas Desenhadas/análise , Estabilidade de Medicamentos , Temperatura Alta , Humanos , /urina , Limite de Detecção , Espectrometria de Massas em Tandem/métodos
6.
Forensic Sci Int ; 300: 85-88, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082566

RESUMO

U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance market a few years ago. After incorporating the substance into the urine UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10 autopsy cases within routine case work. In all cases, the cause of death was accidental poisoning by U-47,700 alone or in combination with other psychoactive substances. The concentration of U-47,700 in the blood samples ranged between 0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700 concentration of 0.27 mg/L, no other psychoactive substances were detected. The stored TOF-MS analytical data from the year preceding the incorporation of U-47,700 into the screening was reprocessed in order to search for more positive cases. The data-independent acquisition of the original screening allowed for retrospective re-analysis of the full-scan data without additional experiments on the actual sample. The retrospective data-analysis revealed two additional cases positive for U-47,700. The first mention of U-47,700 on a Finnish internet discussion forum was in March 2015. After having been detected in several death cases, the drug was put under national control in November 2016 and the last fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for approximately 2 years in Finland. Forensic and clinical laboratories need to rapidly adjust their screening procedures in order to adapt to the continuously expanding field of novel psychoactive substances. Retrospective data-analysis is a practical tool for monitoring the emergence of new substances onto the market.


Assuntos
Benzamidas/análise , Drogas Desenhadas/análise , Transtornos Relacionados ao Uso de Opioides/mortalidade , Psicotrópicos/análise , Adulto , Benzamidas/envenenamento , Cromatografia Líquida de Alta Pressão , Drogas Desenhadas/envenenamento , Finlândia/epidemiologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Espectrometria de Massas , Psicotrópicos/envenenamento , Adulto Jovem
7.
J Forensic Leg Med ; 65: 92-100, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128567

RESUMO

In Hungary, N-ethyl-hexedrone (NEH) was the most frequently seized stimulant designer drug in 2017, while among synthetic cannabinoids ADB-FUBINACA and AB-FUBINACA were the most popular. Symptoms of intoxication by these substances are well known but less is known about the pathology of overdose-related death. NEH-induced fatal intoxication has not been described in the literature and knowledge surrounding the particular circumstances of death could be useful better public education of risk and more adequate treatment of overdose patients. In this report, we characterize the case of a 23-year-old male regular drug user who died a few hours after NEH and ADB-FUBINACA consumption. His medical history showed arrhythmia in childhood, and some seizures. Autopsy found he had a BMI of 42.9, a hypertrophic and dilated heart, severe atherosclerosis of the valves, coronaries and the arteries, and edema of the internal organs. Histology confirmed those findings. Postmortem blood levels of NEH were 285 ng/ml, along with 0.08 ng/ml ADB-FUBINACA and five ADB-FUBINACA metabolites. Based on the blood concentrations measured in suspected drug users (≤83.9 ng/ml) we hypothesize that NEH intoxication was the cause of death in this case, with heart disease being a co-factor and that the synthetic cannabinoid effect might have been accompaniment. This case also offered the opportunity to identify the metabolites of ADB-FUBINACA in the blood. We identified metabolites in the post-mortem blood by comparing them to human liver microsomal enzyme metabolites in vitro. Three major and two minor metabolites were found in the blood, of which two could only be derived from ADB-FUBINACA, as opposed to other cannabinoids. The case highlights the importance of the complex analysis of drug related deaths by medico-legal autopsy, histopathology and toxicology.


Assuntos
Alcaloides/envenenamento , Canabinoides/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Drogas Desenhadas/envenenamento , Indazóis/envenenamento , Alcaloides/sangue , Canabinoides/sangue , Cardiomiopatia Dilatada/patologia , Estimulantes do Sistema Nervoso Central/sangue , Cromatografia Líquida , Drogas Desenhadas/análise , Overdose de Drogas , Usuários de Drogas , Humanos , Indazóis/sangue , Rim/patologia , Masculino , Espectrometria de Massas/métodos , Edema Pulmonar/patologia , Detecção do Abuso de Substâncias , Adulto Jovem
8.
J Forensic Leg Med ; 65: 101-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129558

RESUMO

Structural analogs of classic drugs, also called designer drugs, are a booming market due to the easy accessibility on the internet and their legal status. One of those 'legal highs' is an analog of phencyclidine, namely 3-methoxyphencyclidine (3-MeO-PCP). Very few fatalities have been reported where 3-MeO-PCP contributed to the death of an individual. We present the first fatal case in the Netherlands and one of the few worldwide. Postmortem biological samples and the presumed abused unknown substance, sold as ant poison, were obtained. 3-MeO-PCP was detected, and the resulting concentration was 152 µg/l in whole blood. The presumed taken unknown sample was identified as 3-MeO-PCP and thus linked to the victim. The cause of death was a combination of 3-MeO-PCP, amphetamine, and alcohol. Improved diagnostic skills are necessary to face these emerging novel psychoactive substances also in light of public health and social risks.


Assuntos
Drogas Desenhadas/envenenamento , Fenciclidina/análogos & derivados , Psicotrópicos/envenenamento , Adulto , Anfetamina/sangue , Concentração Alcoólica no Sangue , Cromatografia Líquida , Drogas Desenhadas/análise , Humanos , Masculino , Espectrometria de Massas/métodos , Países Baixos , Fenciclidina/sangue , Fenciclidina/envenenamento , Psicotrópicos/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue
9.
Forensic Sci Int ; 300: e34-e37, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31056341

RESUMO

The significant increase in the number of new psychoactive substances on the drug market has recently been a serious problem. The manuscript presents a fatal case of suicide poisoning with 3-MMC (3-methylmethcathinone). The biological material collected during the autopsy of a 19-year-old woman, transferred to the toxicological Laboratory in Katowice ToxLab, was subjected to a chemical and toxicological analysis. The toxicological analysis of blood, vitreous humor and gastric contents revealed 3-methylmetcatinone at a concentration of 800 ng/ml, 153 ng/ml and 5,5 mg, respectively. The presence of 3-MMC has also been confirmed in physical evidence secured on site. 3-methylmethcathinone is a dangerous psychoactive substance that caused the death of the 19-year-old.


Assuntos
Drogas Desenhadas/envenenamento , Metanfetamina/análogos & derivados , Psicotrópicos/envenenamento , Drogas Desenhadas/análise , Feminino , Conteúdo Gastrointestinal/química , Humanos , Metanfetamina/análise , Metanfetamina/envenenamento , Psicotrópicos/análise , Suicídio , Corpo Vítreo/química , Adulto Jovem
10.
Forensic Sci Int ; 301: e29-e37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31138461

RESUMO

5F-ADB is an indazole-based synthetic cannabinoid. In recent years, it has been detected in legal high products as well as in biological samples and is associated with serious adverse health, behavioral effects and even death. Due to the fast pace of the market of synthetic cannabinoids, data on such newly appearing substances are scarce. As pharmacological properties are often investigated in vitro or by using animal experiments, reports on synthetic cannabinoid findings in human samples along with corresponding case history descriptions are valuable for the interpretation of upcoming routine cases. Herein we report five cases with verified 5F-ADB consumption, including three fatalities, a case of driving under the influence of drugs as well as a case of grievous bodily harm. In four cases, 5F-ADB could be detected in blood or plasma. Concentrations were in the range of 0.11-0.57 µg/L. In one instance 5F-ADB consumption was verified by the detection of 5F-ADB metabolites in postmortem body fluids. The described cases illustrate various adverse effects including confusion (possibly even psychosis), collapse, loss of consciousness, unsafe driving style or changing moods that might be attributed to 5F-ADB.


Assuntos
Canabinoides/envenenamento , Drogas Desenhadas/envenenamento , Adolescente , Adulto , Canabinoides/análise , Canabinoides/química , Confusão/induzido quimicamente , Drogas Desenhadas/análise , Drogas Desenhadas/química , Dirigir sob a Influência , Evolução Fatal , Feminino , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Comportamento Autodestrutivo/induzido quimicamente , Detecção do Abuso de Substâncias , Inconsciência/induzido quimicamente
11.
Drug Test Anal ; 11(7): 1109-1115, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30892803

RESUMO

A liquid chromatography-mass spectrometry (LC-MS) screen for known anabolic-androgenic steroids in a dietary supplement product marketed for "performance enhancement" detected an unknown compound having steroid-like spectral characteristics. The compound was isolated using high performance liquid chromatography with ultraviolet detection (HPLC-UV) coupled with an analytical scale fraction collector. After the compound was isolated, it was then characterized using gas chromatography with simultaneous Fourier Transform infrared detection and mass spectrometry (GC-FT-IR-MS), liquid chromatography-high resolution accurate mass-mass spectrometry (LC-HRAM-MS) and nuclear magnetic resonance (NMR). The steroid had an accurate mass of m/z 285.1847 (error-0.57 ppm) for the protonated species [M + H]+ , corresponding to a molecular formula of C19 H24 O2 . Based on the GC-FT-IR-MS data, NMR data, and accurate mass, the compound was identified as androsta-3,5-diene-7,17-dione. Although this is not the first reported identification of this designer steroid in a dietary supplement, the data provided adds information for identification of this compound not previously reported. This compound was subsequently detected in another dietary supplement product, which contained three additional active ingredients.


Assuntos
Androstadienos/análise , Drogas Desenhadas/análise , Suplementos Nutricionais/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Detecção do Abuso de Substâncias
12.
Forensic Sci Int ; 298: 186-267, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30925344

RESUMO

In the last decades, more and more new psychoactive substances (NPS) were introduced on the drug market which were sold as "legal" alternatives for classic drugs and misused medications. Due to an increased number of available substances and a growing utilization by users of common drugs but also by inexperienced users because of the supposed "legal" status, also undesired adverse effects of these NPS, at worst leading to death, became apparent. This review summarizes fatalities previously described in scientific literature which were attributed to the use of NPS or such cases, in which intake of NPS was proven or even assumed to contribute to death. This summary includes an overview of substances involved (particularly synthetic cannabinoids ("spice"), novel opioids and synthetic cathinones ("bath salts")) as well as of postmortem concentrations determined in various biological matrices. The compiled data assist forensic toxicologists with the interpretation of death cases involving NPS.


Assuntos
Drogas Desenhadas/efeitos adversos , Psicotrópicos/efeitos adversos , Alcaloides/efeitos adversos , Alcaloides/análise , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/análise , Canabinoides/efeitos adversos , Canabinoides/análise , Drogas Desenhadas/análise , Humanos , Psicotrópicos/análise
13.
Forensic Sci Int ; 297: 372-377, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850157

RESUMO

Synthetic cannabinoids (SCs) belong to the group of new psychoactive substances (NPS) which appear sprayed on herbal mixtures on the "street" drug market and are intended for smoking like marijuana. In the present report we discuss a fatal case of 18-years-old boy, who had smoked SCs since several months and an overuse of SCs during last 48 h of his life has been apprised. The autopsy findings revealed acute respiratory distress syndrome (ARDS). Both toxicological analysis of deceased blood and urine samples and chemical analysis of the herbal mixture seized revealed presence of two SCs - 5F-ADB and FUB-AMB. The amount of 5F-ADB in blood was found to be 3.7 ng/mL by standard addition method. Severe and irreversible morphology changes in lung specimen, leading to ischemic damage of all internal organs and tissues, were observed during histological examination. The present case can be discussed as an example of both drug-induced and drug-related death resulting from acute intoxication with 5F-ADB and FUB-AMB as well as from systematic use of both synthetic cannabinoids.


Assuntos
Canabinoides/efeitos adversos , Drogas Desenhadas/efeitos adversos , Indazóis/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Valina/análogos & derivados , Adolescente , Canabinoides/sangue , Canabinoides/urina , Drogas Desenhadas/análise , Overdose de Drogas , Humanos , Indazóis/sangue , Indazóis/urina , Extração Líquido-Líquido , Pulmão/patologia , Masculino , Transtornos Relacionados ao Uso de Substâncias/complicações , Valina/efeitos adversos , Valina/sangue , Valina/urina
14.
Forensic Sci Int ; 298: 115-120, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30897447

RESUMO

A multi-analyte method for detection and quantification of 16 synthetic cathinones (known also as "bath salts") in human hair has been developed and fully validated using liquid chromatography-tandem mass spectrometry system. About 20 mg of hair samples, previously washed and homogenized, were ultrasonicated with 1 mL HCl 0.1 M solution. Samples were then extracted using a solid phase extraction procedure (SPE), taken to dryness and reconstituted in 100 µL mobile phase. Finally, they were directly injected into a liquid chromatographic system, coupled with tandem mass spectrometer detector. The validation criteria parameters were satisfactory according with the international guidelines. A LOQ of 5 pg/mg was obtained for 4-fluoromethcathinone (4-FMC), buphedrone, ethcathinone, methcathinone, mephedrone and naphyrone, while the method proved to be more sensitive for 4-methylethcathinone (4-MEC), methedrone, alpha-pyrrolidinopentiophenone (α-PVP), alpha-pyrrolidinohexiophenone (α-PHP), methylenedioxypyrovalerone (MDPV), butylone, ethylone, 3,4-dimethylmethcathinone (3,4-DMMC), pentedrone and pentylone, reaching a LOQ of 1 pg/mg. Potential use of bath salts was investigated in postmortem cases of young subjects previously tested positive at least to one traditional drug of abuse. Two samples out of 17 cases analyzed provided positive results for synthetic cathinones. One sample has been divided in two segments of 2.5 cm length each. Both segments were positive for 8 different cathinone derivatives, namely: 3,4-DMMC, 4-FMC, 4-MEC, α-PHP, α-PVP, methcathinone, methedrone and pentedrone. The second case provided positive results for ethcathinone.


Assuntos
Alcaloides/análise , Drogas Desenhadas/análise , Cabelo/química , Detecção do Abuso de Substâncias/métodos , Adolescente , Adulto , Cromatografia Líquida , Feminino , Toxicologia Forense/métodos , Humanos , Limite de Detecção , Masculino , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Espectrometria de Massas em Tandem , Adulto Jovem
15.
Drug Test Anal ; 11(4): 617-625, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730110

RESUMO

The high frequency of the synthetic cannabinoid receptor agonists (SCRAs) emergence renders this group of new psychoactive compounds particularly demanding in terms of detection, identification, and responding. Without the available reference material, one of the specific problems is differentiation and structure elucidation of constitutional isomers. Herein, we report a simple and efficient flow chart diagram applicable for a rapid nuclear magnetic resonance (NMR) identification and differentiation between azaindoles, 4-, 5-, 6-, and 7-azaindole, which is a common structural motif of synthetic cannabinoids. The flow chart diagram is based on 1 H NMR and 1 H-15 N NMR spectra, and to prove the concept, it has been tested on 5F-MDMB-P7AICA (1). Spectral and analytical data including standard 1D and 2D NMR spectra, gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared-attenuated total reflectant (FTIR-ATR), Raman, melting point, and combustion analysis are provided for compound 1.


Assuntos
Canabinoides/análise , Drogas Desenhadas/análise , Indóis/análise , Psicotrópicos/análise , Agonistas de Receptores de Canabinoides/análise , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Drug Test Anal ; 11(2): 223-229, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30109775

RESUMO

Designer benzodiazepines have emerged as recreational drugs. They are available via the Internet without control and are found in the form of falsified (fake) medicines. For some of them, limited information concerning their effects, their toxicity, and their detection in bio fluids is available in the literature. For others, nothing has been published, as in the case of flunitrazolam (FNTZ). To gain preliminary data on its elimination parameters in urine and to investigate its metabolism, one of the authors ingested one pink tablet bought on the Internet, after confirming the absence of other compounds and agreement with the labeled dosage (0.25 mg) by nuclear magnetic resonance (NMR). A software algorithm (MetaboLynx, Waters, Milford, MA, USA) was used to predict FNTZ biotransformation and four potential metabolites were proposed: 4-hydroxy-FNTZ, desnitro-FNTZ, 7-amino-FNTZ, and 7-acetamido-FNTZ. Urine samples were collected over 72 hours following oral administration of one tablet. After liquid/liquid extraction at pH 9.5, FNTZ concentrations were determined using ultra performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QqQ-MS/MS). FNTZ remained detectable in hydrolyzed urine for 21 hours after ingestion, with concentrations ranging between 1 and 18 ng/mL. About 3% of the initial dose was excreted in urine as total unchanged FNTZ during this period. In vitro experiments (HLM incubations) were performed using ultra performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-QTOF-MS) in order to investigate the potential CYP- and UGT-dependent metabolites where only 7-amino-FNTZ was detected as the only metabolite. However, in the urine specimens, desnitro-FNTZ, 7-acetamido-FNTZ and 7-amino-FNTZ were the main detected compounds. The identification of FNTZ metabolites dramatically improves the detection windows of the drug up to 37 hours.


Assuntos
Benzodiazepinas/metabolismo , Benzodiazepinas/urina , Drogas Desenhadas/análise , Drogas Desenhadas/metabolismo , Detecção do Abuso de Substâncias/métodos , Benzodiazepinas/farmacocinética , Drogas Desenhadas/farmacocinética , Humanos , Fígado/metabolismo
17.
Int J Legal Med ; 133(2): 475-478, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30039274

RESUMO

The abuse of new psychoactive substances (NPS) has been dramatically increasing all around the world since the late 2000s. The availability of hundreds of NPS in the past decade is challenging for both public health and global drug policies. A 39-year-old woman, known as a multidrug addict, was murdered by her partner by ligature strangulation. A comprehensive toxicological screening by gas chromatography and ultra-high performance liquid chromatography with tandem mass spectrometry revealed the simultaneous presence of ethanol (1.37 g/L), diazepam (157 ng/mL) and nordiazepam (204 ng/mL), cocaine (25 ng/mL) and benzoylecgonine (544 ng/mL), and (3-methoxy-(1-(1-phenylcyclohexyl)piperidine) or 3-MeO-PCP, a dissociative hallucinogen anesthetic drug. Concentrations of 3-MeO-PCP were 63, 64, and 94 ng/mL in femoral blood, bile, and urine, respectively. Hair tested also positive for 3-MeO-PCP on 3 × 2-cm segments at 731, 893, and 846 pg/mg, indicating long-term abuse of the drug. This seems to be the first ever reported hair concentrations. Major impairment of the victim, including visual hallucinations and alteration of behavior, was attributed to the mixture of all the drugs, with a major contribution of 3-MeO-PCP. The toxicological findings were compared to the few reports available in the medical literature.


Assuntos
Drogas Desenhadas/análise , Usuários de Drogas , Alucinógenos/análise , Homicídio , Fenciclidina/análogos & derivados , Adulto , Bile/química , Cromatografia Líquida , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/química , Humanos , Fenciclidina/análise , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Espectrometria de Massas em Tandem
18.
Drug Test Anal ; 11(1): 45-50, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29996009

RESUMO

Multiple new psychoactive substances (NPS) are released into the recreational drug market each year. One NPS drug class that has become more common in recent years is that of the benzodiazepines (designer benzodiazepines, DBZ). Several metabolism studies have been performed to improve their bioanalytical detection via the best target. These studies have shown the presence of parent glucuronides and, as polymorphisms have been noted for the catalyzing enzymes (UDP-glucuronyltransferases) responsible for glucuronide conjugation reactions, it is important to keep this in mind when interpreting DBZ cases in clinical and/or forensic toxicology. Therefore, the aim of this study was to determine the UDP-glucuronyltransferases (UGTs) responsible for parent compound conjugation of nine DBZ to facilitate interpretation of related cases. Clonazolam, deschloroetizolam, etizolam, flubromazolam, flunitrazolam, metizolam, nifoxipam, nitrazolam, and pyrazolam were incubated with pooled human liver microsomes (pHLM) or 13 different human UGTs. The samples were analyzed using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). Glucuronide conjugates of flunitrazolam and nifoxipam were only detected in pHLM, suggesting that these reactions are performed by dimer complexes of several UGTs or complexes between UGTs and other metabolizing enzymes contained in pHLM. Nitrazolam or pyrazolam glucuronides were not detected. Glucuronidation of clonazolam, deschloroetizolam, etizolam, flubromazolam, and metizolam was catalyzed exclusively by UGT1A4. The conjugation of the majority of the DBZ was performed by the UGT isoform 1A4 for which polymorphisms have been described. This underlines the importance of taking glucuronidation polymorphism into consideration when interpreting intoxication cases.


Assuntos
Benzodiazepinas/metabolismo , Drogas Desenhadas/metabolismo , Glucuronídeos/metabolismo , Glucuronosiltransferase/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Benzodiazepinas/análise , Benzodiazepinas/química , Cromatografia Líquida/métodos , Drogas Desenhadas/análise , Drogas Desenhadas/química , Glucuronídeos/química , Glucuronosiltransferase/química , Humanos , Insetos , Microssomos/metabolismo , Detecção do Abuso de Substâncias/métodos
19.
J Anal Toxicol ; 43(3): 170-178, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295842

RESUMO

Novel psychoactive substances (NPS) are emerging drugs of abuse that are variations of existing compounds intended to cause a CNS psychotropic effect. Some NPS are so comparable in structure and physicochemical properties that they co-elute using traditional single column chromatographic techniques and therefore will not be detected as individual compounds. 2D liquid chromatography (2D-LC) has demonstrated applicability in difficult separations of small molecules and compounds in complex mixtures. It was hypothesized that this technique could also be used to separate co-eluting isomeric and structurally related, non-isomeric NPS, including synthetic cannabinoids (SC). Initial studies assessed several parameters, including column type, mobile phase, analysis time, gradient and flow rate, to optimize a 2D-LC method for separation and analysis of SC. The final comprehensive on-line 2D-LC method employed a Bonus-RP column in the first dimension (1D) coupled with UV detection and a biphenyl column in the second dimension (2D) coupled with QTOF-MS detection in full scan positive mode. To test the utility of the method, three SC mixes were created, each containing five compounds that were unresolvable in a traditional, 1D-LC separation; one mix with isomeric compounds and two with structurally related but non-isomeric compounds. Contour plots of UV absorbance in 1D and MS ion intensity in 2D demonstrated that all components in each mixture were successfully resolved using the 2D-LC separation method. This research serves as proof-of-concept for the application of 2D-LC to the separation of isomeric and structurally related SC. With further optimization and validation, 2D-LC may be a generally useful tool for separation of complex mixtures of NPS.


Assuntos
Canabinoides/análise , Cromatografia Líquida/métodos , Drogas Desenhadas/análise , Espectrometria de Massas/métodos , Psicotrópicos/análise , Canabinoides/química , Fracionamento Químico , Drogas Desenhadas/química , Isomerismo , Estrutura Molecular , Estudo de Prova de Conceito , Psicotrópicos/química , Relação Estrutura-Atividade
20.
Drug Test Anal ; 11(5): 669-677, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30468699

RESUMO

Untargeted toxicological screening is an analytical challenge, given the high number of molecules and metabolites to be detected and the constant appearance of new psychoactive substances (NPS). The combination of liquid chromatography with high-resolution tandem mass spectrometry (HRMS/MS) in a data-dependent acquisition mode generates a large volume of high quality spectral data. Commercial software for processing MS data acquired during untargeted screening experiments usually compare measured features (mass, retention time, and fragmentation spectra) against a predefined list of analytes. However, there is a lack of tools for visualizing and organizing MS data of unknown compounds. Here, we applied molecular networking to untargeted toxicological screening. This bioinformatic tool allows the exploration and organization of MS/MS data without prior knowledge of the sample's chemical composition. The organization of spectral data is based on spectral similarity. Hence, important information can be obtained even before the annotation step. The link established between molecules enables the propagation of structural information. We applied this approach to three clinical and forensic cases with various matrices: (a) blood and a syringe content in a forensic case of death by self-injection, (b) hair segments in a case of drug-facilitated assault, and (c) urine and blood samples in a case of 3-methoxyphencyclidine intoxication. Data preprocessing with MZmine allows sample-to-sample comparison and generation of multisample molecular networks. Our present study shows that molecular networking can be a useful complement to conventional approaches for untargeted screening interpretation, for example for xenobiotics identification or NPS metabolism elucidation.


Assuntos
Clormequat/análise , Drogas Desenhadas/análise , Doxilamina/análise , Toxicologia Forense/métodos , Fenciclidina/análogos & derivados , Adolescente , Antieméticos/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenciclidina/análise , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
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