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1.
Tidsskr Nor Laegeforen ; 144(4)2024 Mar 19.
Artigo em Norueguês | MEDLINE | ID: mdl-38506014

RESUMO

Background: The knowledge base on new psychoactive substances (NPS) is generally limited. This introduces new challenges and increased unpredictability in substance abuse treatment. Case presentation: A man in his thirties was submitted to detoxification after reportedly using flubromazolam, a high potency designer benzodiazepine, which he had purchased on the dark web. Extensive drug testing of serum, urine and hair, and the remains in a dropper bottle delivered by the patient, did not reveal flubromazolam or possible metabolites, but did reveal several common drugs of abuse, and 8-aminoclonazolam, a metabolite of clonazolam, another designer benzodiazepine sold on the dark web. The detoxification was uncomplicated. An excessive treatment protocol based on the patient's information, involving high preparedness and increased resources, both clinically and analytically, turned out to be unnecessary. Interpretation: The drug use and clinical course in this case proved to be more common than the unit prepared for. The case history illustrates both the challenges with users of NPS and the general unpredictability in substance abuse treatment.


Assuntos
Drogas Desenhadas , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Benzodiazepinas/efeitos adversos , Detecção do Abuso de Substâncias/métodos , Psicotrópicos
2.
J Pharm Biomed Anal ; 243: 116086, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38518457

RESUMO

The use of new psychoactive substances derived from ketamine is rarely reported in France. A chronic GHB, 3-MMC, and methoxetamine consumer presented a loss of consciousness in a chemsex context and was referred to the intensive care unit with a rapid and favorable outcome. To investigate the chemicals responsible for the intoxication, a comprehensive analysis was conducted on the ten plasma samples collected over a 29.5-hour period, urine obtained upon admission, a 2-cm hair strand sample, and a seized crystal. These analyses were performed using liquid chromatography hyphenated to high resolution tandem mass spectrometry operating in targeted and untargeted modes. Additionally, analyses using gas chromatography coupled to mass spectrometry and nuclear magnetic resonance were conducted to probe the composition of the seized crystal. The molecular network-based approach was employed for data processing in non-targeted analyses. It allowed to confirm a multidrug exposure encompassing GHB, methyl-(aminopropyl)benzofuran (MAPB), (aminopropyl)benzofuran (APB), methylmethcathinone, chloromethcathinone, and a new psychoactive substance belonging to the arylcyclohexylamine family namely deschloro-N-ethyl-ketamine (O-PCE). Molecular network analysis facilitated the annotation of 27 O-PCE metabolites, including phase II compounds not previously reported. Plasma kinetics of O-PCE allowed the estimation of the elimination half-life of ∼5 hours. Kinetics of O-PCE metabolites was additionally characterized, possibly useful as surrogate biomarkers of consumption. We also observed marked alterations in lipid metabolism related to poly consumption of drugs. In conclusion, this case report provides a comprehensive analysis of exposure to O-PCE in a multidrug user including kinetic and metabolism data in human.


Assuntos
Benzofuranos , Oxibato de Sódio , Humanos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Toxicocinética , Oxibato de Sódio/análise , Espectrometria de Massas em Tandem , Detecção do Abuso de Substâncias/métodos
3.
Forensic Sci Int ; 357: 111990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518566

RESUMO

In order to investigate the influences of hair dyeing on the distribution shapes of drugs in hair, different hair dyeing processes ("semi-permanent coloring without bleaching" and "permanent coloring with bleaching") were performed in vitro on black hair specimens collected from two subjects (Asians) who took a single dose of zolpidem (ZP, 10 mg of ZP tartrate) or methoxyphenamine (MOP, 50 mg of MOP hydrochloride). Under the following three different dyeing conditions, (1) semi-permanent coloring, (2) permanent coloring (once), (3) permanent coloring (twice), drug distributions in single hair specimens were investigated using a 2-mm segmental analysis by liquid chromatography-tandem mass spectrometry. Distribution shapes of drugs changed significantly only under the permanent coloring (twice) condition, resulting in reduced peak concentration and extended distribution width. There was, however, no significant difference in the amounts of drugs in hair between non-treated and dyed specimens, suggesting the drugs hardly leaked out of hair or were only slightly degraded during dyeing. In addition, while assuming contact with aqueous environment such as daily hair washing after dyeing, dyed hair specimens were individually immersed in ultrapure water for 20 hours, then the outflow of drugs in ultrapure water as well as the distribution shapes of drugs remaining in hair were determined. The drug outflow after permanent coloring (once and twice) was significantly larger than those after semi-permanent coloring, and the outflow ratios, [outflow]/([outflow] + [amount remaining in hair]), ranged over 9.8-24% (n = 3) for ZP and 68-71% (n = 3) for MOP after permanent coloring (once), and 54-72% (n = 3) for ZP and 86-91% (n = 3) for MOP after permanent coloring (twice). The distribution shapes of drugs after 20 h of immersion tended to flatten as outflow ratios increased, resulting in no change in the shapes after semi-permanent coloring, and complete collapse of their shapes after permanent coloring (twice). Thus, the present results indicated that hair dyeing involving bleaching and subsequent contact with aqueous environment after dyeing could significantly influence distribution shapes of drugs in hair.


Assuntos
Cabelo , Metanfetamina/análogos & derivados , Detecção do Abuso de Substâncias , Humanos , Zolpidem/análise , Detecção do Abuso de Substâncias/métodos , Cabelo/química , Água/análise
4.
Clin Chim Acta ; 557: 117879, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38499138

RESUMO

The presence of ostarine, a selective androgen receptor modulator (SARM) in an athlete's urine specimen constitutes one of the most frequent anti-doping rules violation as the drug is listed as a member of the S1.2 class "other anabolic agents" of the World Anti-doping Agency Prohibited List, forbidden in- and out-competition. It is possible to challenge this violation but it is at the charge of the athlete to prove innocence. The conditions to evidence no fault or negligence are mostly based on 2 points: 1. the athlete must present verified circumstances of contamination and the source of contamination must be identified; and 2. there must be verified claims by the athlete that the violation was not intentional. Some months before the Olympic games, a female athlete was suspended by a national anti-doping agency because of an adverse analytical finding for ostarine. She claimed that her violation was due to drug transfer when kissing her boyfriend, who did not inform her about his ostarine daily intake. To document this claim (excretion of ostarine in oral fluid in sufficient amounts), a male volunteer ingested 17.3 mg of ostarine (dose verified by 1H NMR). Oral fluid was collected over 8 h using the NeoSal™ collection device and was tested by liquid chromatography coupled to tandem mass spectrometry. Maximal ostarine concentration was 468 ng/mL at T + 15 min, which can also be partially attributed to mouth contamination. Ostarine was detectable during the whole period of test, with concentrations at 1-2 ng/mL after T + 4 h. These results support drug transfer during kissing and subsequent possible contamination of the partner.


Assuntos
Anilidas , Doping nos Esportes , Humanos , Masculino , Feminino , Cromatografia Líquida/métodos , Androgênios , Administração Oral , Detecção do Abuso de Substâncias/métodos
5.
Clin Chim Acta ; 557: 117871, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38467244

RESUMO

Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs. But in some cases, it can be responsible for an AAF following contamination. We report the case of an athlete who contaminated herself by exchanging body fluids while kissing her boyfriend, who took 25 mg per day of MK-2866 for 9 days prior to the athlete's AAF (urinary concentration evaluated at 13 ng/mL) without her knowledge. Both subjects came to our lab for hair testing. The athlete's hair was black and slightly frizzy. Six segments of 2 cm then 7 × 3 cm (33 cm) were analysed and showed increasing concentrations, from 2 pg/mg on the first segment to 17.8 pg/mg on the last segment. The boyfriend's hair, light-brown, analyzed on 4 × 2 cm, also showed increasing values, from 65 to 143 pg/mg. These gradients of concentration in the hair's athlete and in her boyfriend were compatible with external contamination of the hair, confirmed by analysis of washing baths, pillowcases (150 pg on each), and the athlete's hairbrush (250 pg). Fingernails were also contaminated, with 21 pg/mg in the athlete and 1041 pg/mg in the boyfriend, with highly contaminated washing baths, and toenails were less contaminated, with 2 pg/mg in the athlete and 17.3 pg/mg in the boyfriend. Urine samples taken 35 days after the start of MK-2866 treatment showed a value of 3690 ng/mL in the boyfriend and 5.7 ng/mL in the athlete. After 6 days off, these concentrations were 3.3 ng/mL and 0.1 ng/mL, respectively. A controlled transfer study was carried out 12 days after discontinuation (urine concentrations returned to negative level). After administration of 17 mg (the 25 mg/mL vial having been controlled at 17 mg/mL), urine samples were taken from the boyfriend and the athlete (n = 10 for each) for more than 25 h after they had been living normally with each other (regular kissing in particular). The boyfriend's urine concentrations ranged from 681 ng/mL to 12822 ng/mL (Tmax = 8:30 hrs), and the athlete's from 0.3 ng/mL to 13 ng/mL with Tmax = 8:30 hrs, i.e. at 22:30 hrs, which corresponded exactly to the time of collection of the urine that showed AAF, with a similar concentration. The dose ingested by the athlete was estimated at 15 µg. These results demonstrate the transfer of ostarine via body fluids between two subjects, with a high risk of AAF in one athlete, as observed in our case.


Assuntos
Anabolizantes , Líquidos Corporais , Doping nos Esportes , Humanos , Feminino , Anilidas , Anabolizantes/urina , Líquidos Corporais/química , Detecção do Abuso de Substâncias/métodos
6.
Arh Hig Rada Toksikol ; 75(1): 24-31, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548376

RESUMO

As novel substances, short time windows, and limits of detection increasingly challenge direct methods of doping detection in sports, indirect tools inevitably take a greater role in the fight against it. One such tool is the athlete biological passport (ABP) - a longitudinal profiling of the measured haematological and biochemical biomarkers, combined with calculated scores, against the background of epidemiological data crucial for doping detection. In both of its modules, haematological and steroidal, ABP parameters are analysed with the Bayesian adaptive model, which individualises reference and cut-off values to improve its sensitivity. It takes into account the confounding factors with proven and potential influence on the biomarkers, such as race and altitude exposure. The ABP has already changed the fight against doping, but its importance will further grow with the new modules (e.g., endocrinological), parameters (e.g., plasma volume-independent parameters), and complementing indirect methods (e.g., transcriptomic).


Assuntos
Doping nos Esportes , Esportes , Humanos , Doping nos Esportes/prevenção & controle , Teorema de Bayes , Atletas , Biomarcadores , Detecção do Abuso de Substâncias/métodos
7.
Anal Chem ; 96(12): 4835-4844, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38488022

RESUMO

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.


Assuntos
Aprendizado Profundo , Drogas Ilícitas , Cromatografia Líquida/métodos , Psicotrópicos/análise , Espectrometria de Massas/métodos , Drogas Ilícitas/análise , Detecção do Abuso de Substâncias/métodos
8.
Biosensors (Basel) ; 14(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534233

RESUMO

An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes. The active ingredients in cannabis, termed cannabinoids, affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment. Cannabinoids are a unique class of terpeno-phenolic compounds, with 120 molecules discovered so far. There are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Over the past two decades, there has been a growing research interest in detecting cannabinoids from various biological matrices. There is a need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid as it can reveal the recent intake in comparison with urine specimens, which only show a history of consumption. Significant improvements are continuously made in the analytical formats of various technologies, mainly concerning improving their sensitivity, miniaturization, and making them more user-friendly. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.


Assuntos
Canabinoides , Cannabis , Fumar Maconha , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Saliva , Detecção do Abuso de Substâncias/métodos
9.
J Anal Toxicol ; 48(3): 191-196, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38456706

RESUMO

Due to the increase in the use of novel psychoactive substances (NPS) and their overall prevalence, it is important to have effective and reliable screening technologies to detect NPS in biological matrices. Enzyme-linked immunosorbent assays (ELISA) are among the most popular screening methods. To evaluate the effectiveness of ELISA for NPS detection, five subclasses of NPS (novel synthetic opioids, fentanyl analogs, stimulants, benzodiazepines and hallucinogens) were evaluated in whole blood for their cross-reactivity on commercially available ELISA kits. A variety of novel synthetic opioids were tested at concentrations of 1-80 ng/mL and 50-2000 ng/mL and demonstrated no cross-reactivity to a morphine ELISA plate at either concentration range. Fentanyl analogs were tested at concentrations ranging from 0.01 to 1 ng/mL and had cross-reactivities ranging from 8% to 178% on the fentanyl ELISA kit used. Both para-chloro fentanyl (178%) and acryl fentanyl (164%) showed cross-reactivities well above that of fentanyl. Novel stimulants were tested at concentrations of 0.5-40 ng/mL and 20-2,000 ng/mL. 4-Fluoroamphetamine was the only novel stimulant with cross-reactivity (3,354%) to the amphetamine ELISA plate. Novel benzodiazepines were tested at concentrations of 1-40 ng/mL on a benzodiazepine plate. Cross-reactivities ranged from 36.1% to 263%, with desalkylflurazepam having the highest cross-reactivity. Finally, novel hallucinogens were tested at concentrations of 0.5-10 ng/mL on a phencyclidine (PCP) ELISA plate, which produced no cross-reactivity and then with 10-1,000 ng/mL, which gave results from 56.6% to 151%. Both hydroxy-PCP (151%) and chloro-PCP (137%) showed cross-reactivities above that of PCP. This research has demonstrated the utility of using ELISA-based screening for novel benzodiazepines, hallucinogens and for fentanyl analogs; however, there is limited application and risk of false-negative results for the other drug classes due to low or non-existent cross-reactivities.


Assuntos
Estimulantes do Sistema Nervoso Central , Alucinógenos , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Analgésicos Opioides , Fentanila , Anfetamina/análise , Benzodiazepinas , Detecção do Abuso de Substâncias/métodos
10.
Clin Lab ; 70(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38469763

RESUMO

BACKGROUND: Substance use is an important public health problem and increasing all over the world. Different methods have been defined for drug abuse testing in medical laboratories. We aimed to compare two urine drug screening methods with liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: A total of 102 patients' urine samples were analyzed by test dip card and EMIT (enzyme multiplied im-munoassay technique). Randomly selected samples (n = 51; 50%) were also analyzed by LC-MS/MS as the reference method. RESULTS: The drug results of all patients analyzed with the test card and EMIT were compatible. Nine of 51 samples (18%) were negative according to all methods. The sensitivity and specificity percentages of AMP, COC, MDMA, OPI/MOP, and THC using test card were 70/96, 100/100, 47/100, 50/100, and 80/85, respectively. Similarly, the sensitivity and specificity percentages of AMP, COC, MDMA, OPI/MOP, and THC using EMIT were 76/97, 100/100, 57/100, 56/100, and 76/91, respectively. CONCLUSIONS: The performances of two immunochemical methods were similar for AMP, BZO, COC, MDMA, OPI/MOP, and THC whereas lower than LCMS/MS for AMP, MDMA, OPI/MOP, and THC. A sample that is positive according to any immunochemical method should be confirmed by definitive techniques such as LC-MS/MS.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Detecção do Abuso de Substâncias , Humanos , Detecção do Abuso de Substâncias/métodos , N-Metil-3,4-Metilenodioxianfetamina/urina , Cromatografia Líquida , Espectrometria de Massas em Tandem , Sensibilidade e Especificidade
11.
Molecules ; 29(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38474487

RESUMO

A method was developed for the determination of 26 drugs of abuse from different classes, including illicit drugs in quantitative dried blood spots (qDBSs), with the aim to provide a convenient method for drug testing by using only 10 µL of capillary blood. A satisfactory limit of quantification (LOQ) of 2.5 ng/mL for 9 of the compounds and 5 ng/mL for 17 of the compounds and a limit of detection (LOD) of 0.75 ng/mL for 9 of the compounds and 1.5 ng/mL for 17 of the compounds were achieved for all analytes. Reversed-phase liquid chromatography was applied on a C18 column coupled to MS, providing selective detections with both +ESI and -ESI modes. Extraction from the qDBS was performed using AcN-MeOH, 1:1 (v/v), with recovery ranging from 84.6% to 106%, while no significant effect of the hematocrit was observed. The studied drugs of abuse were found to be stable over five days under three different storage conditions (at ambient temperature 21 °C, at -20 °C, and at 35 °C), thus offering a highly attractive approach for drug screening by minimally invasive sampling for individuals that could find application in forensic toxicology analysis.


Assuntos
Teste em Amostras de Sangue Seco , 60705 , Humanos , Teste em Amostras de Sangue Seco/métodos , Limite de Detecção , Detecção do Abuso de Substâncias/métodos , Cromatografia de Fase Reversa , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodos
12.
Sud Med Ekspert ; 67(1): 56-61, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38353016

RESUMO

Quantitative determination of ethyl glucuronide (EtG) in different biological objects in recent years has been positioned as one of the most reliable biomarkers of unconditional alcohol consumption. The aim of the study is to summarize the analytical methods of alcohol consumption testing with the use of EtG currently available in domestic and foreign literature and to present a schematic overview of possible errors in reproducibility and interpretation of research on EtG results, which may limit their use in forensic medical practice. The main objective is to increase the reliability and validity of EtG as a marker of ethanol consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Detecção do Abuso de Substâncias , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/métodos , Glucuronatos , Biomarcadores , Etanol
13.
Anal Methods ; 16(8): 1133-1149, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38314866

RESUMO

Cannabis and associated substances are some of the most frequently abused drugs across the globe, mainly due to their anxiolytic and euphorigenic properties. Nowadays, the analysis of hair samples has been given high importance in forensic and analytical sciences and in clinical studies because they are associated with a low risk of infection, do not require complicated storage conditions, and offer a broad window of non-invasive detection. Analysis of hair samples is very easy compared to the analysis of blood, urine, and saliva samples. This review places particular emphasis on methodologies of analyzing hair samples containing cannabis, with a special focus on the preparation of samples for analysis, which involves screening and extraction techniques, followed by confirmatory assays. Through this manuscript, we have presented an overview of the available literature on the screening of cannabis using mass spectroscopy techniques. We have presented a detailed overview of the advantages and disadvantages of this technique, to establish it as a suitable method for the analysis of cannabis from hair samples.


Assuntos
Cannabis , Alucinógenos , Drogas Ilícitas , Humanos , Detecção do Abuso de Substâncias/métodos , Alucinógenos/análise , Drogas Ilícitas/análise , Agonistas de Receptores de Canabinoides/análise , Cabelo/química
14.
J Pharm Biomed Anal ; 241: 115996, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330785

RESUMO

BACKGROUND AND AIM: Non-medical use of Pregabalin (PGB) is a growing concern in many countries because of the serious consequences associated with their abuse. Judicial cases within the probation system, multiple drug users, and patients in treatment programs administered PGB at higher doses than suggested, commonly without prescription. For this reason, it is important to analyze PGB by adding it to the routine analysis scale in determining whether PGB is used for medical purposes or abuse. In this study, PGB analyzed (single or multiple substance use, concomitant substances) in urine samples of forensic and clinical cases by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition to the sociodemographic and clinical characteristics of pregabalin-positive cases, the results were evaluated separately from a clinical and forensic perspective. METHODS: All urine samples which was admitted to Addiction Toxicology Laboratory from 'drug abuse probation system' (forensic cases, n = 640) and from various departments of our hospital (clinical cases, n = 371) between December 2022 and April 2023. Screening analysis were carried out by immunoassay in total 1011 cases. LC-MS/MS method simultaneously analyzed amphetamine, benzoilecgonine, cocaine, codeine, metamphetamine, morphine, 3,4-metilenedioksi-N-metilamfetamin (MDMA), 11-nor-9-karboksi-Δ9-tetrahidrokannabinol and pregabalin in urine samples. PGB was added to the our routine substance screening analysis scale in December 2022 to detect pregabalin use. RESULTS: PGB was detected in 12.3% of probabition cases and 13.2% of clinical cases. The mean age of PGB positive cases was 26.55 ± 7,52 years old, predominantly males (%85,9). Single PGB was detected in 53.2% of forensic cases (n = 42), and 38.7% of clinical cases (n = 19). The most common substance detected concomitantly with PGB was amphetamine type stimulants (ATSs:amphetamine, methamphetamine, ecstasy/MDMA etc.) (22.8% of forensic cases and 46.9% of clinical cases), followed by concomitant cannabis use (24.1% of forensic cases and 26.5% of clinical cases). Concomitant opioid use was rare (1.3% of forensic cases and 4.1% of clinical cases). Detection of PGB was significantly different across months on which the samples were collected (x2 = 82.8, df=4, p < 0.001). CONCLUSION: Inconsistently with previous studies suggesting opioids as the most prevalant substances concominant with PGB, our results showed that stimulants (especially ATSs) were the most prevelant substances concominant with PGB, followed by cannabis. High proportion of PGB detection in probabition cases, frequently as a single substance abuse takes attention. These results suggest that PGB, may be used to avoid legal consequences. It is important for laboratories to be aware that they need to make changes as addition of newly abused substances in their analysis panels, when necessary, as differences between regions and cultures affect substance use patterns.


Assuntos
Estimulantes do Sistema Nervoso Central , Alucinógenos , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Feminino , N-Metil-3,4-Metilenodioxianfetamina/análise , Pregabalina , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Anfetamina/urina , Estimulantes do Sistema Nervoso Central/urina , Alucinógenos/análise , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Detecção do Abuso de Substâncias/métodos
15.
Clin Toxicol (Phila) ; 62(1): 10-18, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38421358

RESUMO

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.


Assuntos
Pálpebras , Alucinógenos , Abuso de Maconha , Detecção do Abuso de Substâncias , Adulto , Humanos , Cannabis , Pálpebras/efeitos dos fármacos , Fumar Maconha , Reprodutibilidade dos Testes , Tremor/induzido quimicamente , Tremor/diagnóstico , Abuso de Maconha/diagnóstico , Detecção do Abuso de Substâncias/métodos
16.
J Pharm Biomed Anal ; 243: 116054, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38422647

RESUMO

INTRODUCTION: In the dynamic universe of new psychoactive substances (NPS), the identification of multiple and chemically diverse compounds remains a challenge for forensic laboratories. Since hair analysis represents a gold-standard to assess the prevalence of NPS, which are commonly detected together with classical drugs of abuse (DoA), our study aimed at developing a wide-screen method to detect and quantify 127 NPS and 15 DoA on hair. MATERIALS AND METHODS: A multi-analyte ultra-high performance liquid chromatography mass spectrometry method for the identification and quantification of 127 NPS (phenethylamines, arylcyclohexylamines, synthetic opioids, tryptamines, synthetic cannabinoids, synthetic cathinones, designer benzodiazepines) and 15 DoA in hair samples was developed. A full validation was performed according to the European medicines Agency (EMA) guidelines, by assessing selectivity, linearity, accuracy, precision, limit of quantification (LOQ), limit of detection (LOD), matrix effect and recovery. As a proof of the applicability, the method was applied to 22 authentic hair samples collected for forensic purposes. RESULTS: Successful validation was achieved, by meeting the required technical parameters, for 137 compounds (122 NPS and 15 DoA), with LOQ set at 4 pg/mg for 129 compounds, at 10 pg/mg for 6 and at 40 pg/mg for 2. The method was not considered validated for 5 NPS, as LLOQ resulted too high for a forensic analysis (80 pg/mg). Among authentic forensic samples, 17 tested positive for DoA, and 10 to NPS, most samples showing positivity for both. Detected NPS were ketamine and norketamine, 5-MMPA, ritalinic acid, methoxyacetyl fentanyl, methylone and RCS-4. CONCLUSION: The present methodology represents an easy, low cost, wide-panel method for the quantification of 122 NPS and 15 DoA, for a total of 137 analytes, in hair samples. The method can be profitably applied by forensic laboratories. Similar multi-analyte methods on the hair matrix might be useful in the future to study the prevalence of NPS and the co-occurrence of NPS-DoA abuse.


Assuntos
Canabinoides , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Detecção do Abuso de Substâncias/métodos , Drogas Ilícitas/análise , Analgésicos Opioides/análise , Canabinoides/análise , Cabelo/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-38387341

RESUMO

In 2017, higenamine was added to the World Antidoping Agency's (WADA) Prohibited list under group S3: beta-2 agonists and it is banned for athletes both in - and out of competition. Aim of this study was to characterize the urinary excretion profile of higenamine and its metabolite coclaurine after oral administration of multiple doses of higenamine capsules. For this purpose, an administration study including female basketball players was performed. For the detection of higenamine and cocalurine in the collected urine samples, a new, fast, and highly sensitive quantitative on-line SPE LC HRMS method was developed and validated. The method was applied for the quantification of higenamine and cocalurine in urine and their excretion pattern was defined. Results obtained show substantial inter-individual differences in the excretion profile of higenamine and coclaurine. For higenamine, half-lives were estimated to be between 4 and 27 h, and for coclaurine between 5 and 25 h. Furthermore, the data indicate that the elimination of coclaurine is rate-limited by its formation. Higenamine could be detected at a urine concentration above 10 ng/mL for at least 20 h after the last application for all study participants.


Assuntos
Alcaloides , Doping nos Esportes , Tetra-Hidroisoquinolinas , Humanos , Feminino , Tetra-Hidroisoquinolinas/urina , Alcaloides/urina , Administração Oral , Detecção do Abuso de Substâncias/métodos
19.
Forensic Sci Int ; 356: 111966, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367459

RESUMO

Amphetamine-type stimulants are the third most widely consumed category of illicit drugs worldwide. Faced with the growing problem of amphetamine-type stimulants, numerous qualitative and quantitative techniques have been developed to detect amphetamine (AMP), methamphetamine (MET), MDMA, MDEA or MDA in biological matrices, including hair. Hair analysis is widely used in forensic medicine, but one of its main drawbacks remains external contamination. In this study, we investigated the possibility of hair contamination through external exposure to blood containing AMP, MET MDMA, MDEA or MDA at 2 ng/mL; 20 ng/mL; 200 ng/mL or 2000 ng/mL after 6 h, 1, 3, 7 or 14 days of contact protected from light at room temperature (RT or 20 °C) or at 4 °C. Dried extracts of hair samples were analyzed by UPLC-MS/MS after extensive washings in several baths of water, methanol and acetone before grounding. At the end of our study, contamination of hair was observed from 6 h of contact with all tested amphetamine-type stimulants. The concentrations found in hair ranged from 3 ± 1 to 1464 ± 10 pg/mg, 5 ± 1 to 5070 ± 160 pg/mg, 3 ± 1 to 1269 ± 60 pg/mg, 4 ± 1 to 1860 ± 113 pg/mg and from 8 ± 1 to 1041 ± 44 pg/mg for AMP, MET, MDMA, MDEA and MDA, respectively. Possibly due to its low polar surface area, MET was the most prone to contaminate. As anticipated, hair contamination was mainly dependent on the concentration of all molecules in the contaminating blood, reaching the SOHT cut-off of 200 pg/mg when amphetamine-type stimulants are at toxic or lethal concentrations in the blood. These observations call for caution in interpreting exposure to these substances in such forensic situations.


Assuntos
3,4-Metilenodioxianfetamina/análogos & derivados , Estimulantes do Sistema Nervoso Central , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Anfetaminas/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem , Detecção do Abuso de Substâncias/métodos , Estimulantes do Sistema Nervoso Central/análise , Cabelo/química
20.
Child Abuse Negl ; 149: 106632, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38368781

RESUMO

BACKGROUND: Previous studies have shown the role of the interaction between the endocannabinoid system (ECS) and life's adversities in the formation of addiction, including alcohol abuse. OBJECTIVE: Our objective was to identify childhood maltreatment (CM) patterns with the strongest impact on the probability of heavy cannabis use (THCCOOH concentrations ≥150 ng/mL) in Iran. PARTICIPANTS AND SETTING: Using survivor sampling, 350 adult participants were selected, and they were then allocated to three categories based on an optimal algorithm: 1) Sexual abuse, 2) Physical abuse, and 3) Physical neglect. METHODS: From 1 September 2019 to 1 May 2023, we implemented a multicenter, matched-pairs, nested, case-control study based on the wave 3-wave 6 data of a longitudinal, multicenter, cohort study. The cases and controls (n = 350 men) were defined according to the severity of CM. The THC potency was evaluated with the delta-9 carboxy tetrahydrocannabinol (THC-COOH) levels in urine using gas chromatography/mass spectrometry (GC/MS). We calculated the population attributable fractions (PAFs) to identify the patterns of maltreatment associated with the highest odds of high-potency cannabis use. RESULTS: Accumulating CM, including sexual abuse, physical abuse, and physical neglect, carried more than three times the risk of heavy cannabis use (OR 3.4 95 % CI 2.9-4.1), and the combination of the three indicators of maltreatment and a high BMI (25-29.9) carried more than four times the risk of heavy cannabis use (OR 4.7 95 % CI 2.7-4.1) compared to the controls. We estimated that in the case of zero CM for each of the three indicators, over 20 % of new cases of heavy cannabis use can be prevented. CONCLUSIONS: The findings show the significance of CM as a predicator of heavy cannabis use in adulthood and in the abstinence phase.


Assuntos
Cannabis , Maus-Tratos Infantis , Abuso de Maconha , Masculino , Adulto , Humanos , Criança , Dronabinol/urina , Abuso de Maconha/epidemiologia , Abuso de Maconha/urina , Estudos de Casos e Controles , Incidência , Estudos de Coortes , Irã (Geográfico)/epidemiologia , Detecção do Abuso de Substâncias
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