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1.
J Anal Toxicol ; 44(7): 708-717, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32808043

RESUMO

An analytical method for the detection of 40 benzodiazepines, (±)-zopiclone, zaleplon and zolpidem in blood and urine by solid-phase extraction liquid chromatography-tandem mass spectrometry was developed and validated. Twenty-nine of 43 analytes were quantified in 0.5 mL whole blood for investigating postmortem, drug-facilitated sexual assault (DFSA) and driving under the influence of drugs cases (DUID). The four different dynamic ranges of the seven-point, linear, 1/x weighted calibration curves with lower limits of quantification of 2, 5, 10 and 20 µg/L across the analytes encompassed the majority of our casework encountered in postmortem, DFSA and DUID samples. Reference materials were available for all analytes except α-hydroxyflualprazolam, a hydroxylated metabolite of flualprazolam. The fragmentation of α-hydroxyflualprazolam was predicted from the fragmentation pattern of α-hydroxyalprazolam, and the appropriate transitions were added to the method to enable monitoring for this analyte. Urine samples were hydrolyzed at 55°C for 30 min with a genetically modified ß-glucuronidase enzyme, which resulted in >95% efficiency measured by oxazepam glucuronide. Extensive sample preparation included combining osmotic lysing and protein precipitation with methanol/acetonitrile mixture followed by freezing and centrifugation resulted in exceptionally high signal-to-noise ratios. Bias and between-and within-day imprecision for quality controls (QCs) were all within ±15%, except for clonazolam and etizolam that were within ±20%. All 29 of the 43 analytes tested for QC performance met quantitative reporting criteria within the dynamic ranges of the calibration curves, and 14 analytes, present only in the calibrator solution, were qualitatively reported. Twenty-five analytes met all quantitative reporting criteria including dilution integrity. The ability to analyze quantitative blood and qualitative urine samples in the same batch is one of the most useful elements of this procedure. This sensitive, specific and robust analytical method was routinely employed in the analysis of >300 samples in our laboratory over the last 6 months.


Assuntos
Benzodiazepinas/metabolismo , Hipnóticos e Sedativos/metabolismo , Detecção do Abuso de Substâncias/métodos , Alprazolam/análogos & derivados , Compostos Azabicíclicos/sangue , Compostos Azabicíclicos/metabolismo , Compostos Azabicíclicos/urina , Benzodiazepinas/sangue , Benzodiazepinas/urina , Cromatografia Líquida/métodos , Diazepam/análogos & derivados , Toxicologia Forense , Humanos , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/urina , Limite de Detecção , Piperazinas/sangue , Piperazinas/metabolismo , Piperazinas/urina , Medicamentos Indutores do Sono/sangue , Medicamentos Indutores do Sono/metabolismo , Medicamentos Indutores do Sono/urina , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Zolpidem/sangue , Zolpidem/metabolismo , Zolpidem/urina
2.
J Anal Toxicol ; 44(7): 718-733, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32672807

RESUMO

A method for analyzing Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-THC (THC-OH) and 11-nor-Δ9-THC-9-carboxylic acid (THC-COOH) in postmortem solid specimens using liquid chromatography-tandem mass spectrometry was developed and validated. A Stomacher instrument was used to prepare these tissues before extraction. Prior to solid phase extraction, liver, kidney, stomach, lung, brain, muscle, bladder and intestine tissues were pretreated with alkaline hydrolysis. All calibration curves were found to be linear with coefficients of determination greater than 0.99. The limit of quantification was 1.0 ng/g. Using three controls, within-run precision ranged between 1.0 and 12.0%, between-run precision ranged between 1.0 and 6.0%, and accuracy ranged between -7.0 and 8.0%. Matrix effects ranged from -21 to 24%. After matrix effects were excluded, analytical recoveries ranged from 79 to 97%. The distributions of THC, THC-OH and THC-COOH were investigated in 32 postmortem cases that tested positive for cannabinoids. This revealed new information regarding the distribution of THC metabolites in stomach, intestine and bladder. Alkaline hydrolysis was sufficient for the deglucuronidation of THC-COOH-glucuronide to its free form, THC-COOH, in all tissues of interest. In conclusion, measuring THC and its metabolites (THC-OH and THC-COOH) in tissues is crucial for any forensic toxicology detection method, especially when bodies are heavily decomposed, as solid tissues may be the only specimens available for testing.


Assuntos
Dronabinol/análise , Toxicologia Forense , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem
3.
J Anal Toxicol ; 44(7): 697-707, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32685960

RESUMO

New psychoactive substances (NPS) are a major public health problem, primarily due to the increased number of acute poisoning cases. Detection of these substances is a challenge. The aim of this research was to develop and validate a sensitive screening method for 104 drugs of abuse, including synthetic cannabinoids, synthetic cathinones, fentanyl analogues, phenethylamines and other abused psychoactive compounds (i.e., THC, MDMA, LSD and their metabolites) in oral fluid by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The Quantisal™ oral fluid device was used to collect oral fluid samples. The oral fluid-elution buffer mixture (500-µL sample) was extracted with t-butyl methyl ether, and chromatographic separation was performed on a Raptor™ biphenyl column (100 × 2.1 mm ID, 2.7 µm), with a total run time of 13.5 min. Limits of detection were established at three concentrations (0.05, 0.1 or 1 ng/mL) for most analytes, except for acetyl norfentanyl and mescaline (5 ng/mL). Matrix effects were generally <20% and overall extraction recoveries >60%. The highest matrix effect was observed within the synthetic cannabinoid group (PB22, -55.5%). Lower recoveries were observed for 2C-T (47.2%) and JWH-175 (58.7%). Recoveries from the Quantisal™ device were also evaluated for all analytes (56.7-127%), with lower recoveries noted for 25I-NBOMe, valerylfentanyl and mCPP (56.7, 63.0 and 69.9%, respectively). Drug stability in oral fluid was evaluated at 15, 60 and 90 days and at 25, 4 and -20°C. As expected, greater stability was observed when samples were stored at -20°C, but even when frozen, some NPS (e.g., synthetic cannabinoids) showed more than 20% degradation. The method was successfully applied to the analysis of seven authentic oral fluid samples positive for 17 different analytes. The method achieved good sensitivity and simultaneous detection of a wide range of NPS.


Assuntos
Drogas Ilícitas/análise , Psicotrópicos/análise , Detecção do Abuso de Substâncias/métodos , Canabinoides , Cromatografia Líquida , Limite de Detecção , Piperazinas , Espectrometria de Massas em Tandem
4.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32581001

RESUMO

Flualprazolam is a nonregistered drug in the benzodiazepine family and constitutes a new psychoactive substance (NPS). Since 2014, a growing number of designer benzodiazepines have become available over the Internet and on the counterfeit drug market. In June 2019, a cluster of patients intoxicated with flualprazolam was identified by the Oregon Poison Center. As an emerging drug of abuse, the clinical characteristics of flualprazolam have been poorly characterized thus far. Over a one-week period, 6 teenagers presented to local emergency departments after ingesting illegally obtained counterfeit alprazolam, which led to sedation. Other symptoms included slurred speech, confusion, and mild respiratory depression. All 6 patients had resolution of their symptoms within 6 hours of ingestion. Blood and urine samples, as well as a tablet fragment, were obtained from 3 patients. The tablet and biological samples were analyzed by using liquid chromatography-quadrupole time-of-flight mass spectrometry and were found to contain the NPS flualprazolam without other drugs or intoxicants. With this case series, we add to the medical literature a clinical description of an emerging drug of abuse. Flualprazolam appears to share the clinical properties of other benzodiazepines. As flualprazolam and other NPSs become more common, physicians must be aware of their availability and characteristics. Sedation lasting <6 hours was observed in 6 of 6 patients exposed to flualprazolam. No effects that would be unexpected from benzodiazepine intoxication were seen among the patients. Specifically, none developed prolonged symptoms or required intubation and mechanical ventilation, ICU admission, or antidotal therapy.


Assuntos
Drogas Desenhadas/efeitos adversos , Centros de Controle de Intoxicações/estatística & dados numéricos , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Surtos de Doenças , Feminino , Hospitalização/tendências , Humanos , Masculino , Espectrometria de Massas , Oregon/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
5.
JAMA ; 323(22): 2310-2328, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515820

RESUMO

Importance: Illicit drug use is among the most common causes of preventable morbidity and mortality in the US. Objective: To systematically review the literature on screening and interventions for drug use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, Embase, and Cochrane Central Register of Controlled Trials through September 18, 2018; literature surveillance through September 21, 2019. Study Selection: Test accuracy studies to detect drug misuse and randomized clinical trials of screening and interventions to reduce drug use. Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 reviewers and random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drug use and other health, social, and legal outcomes. Results: Ninety-nine studies (N = 84 206) were included. Twenty-eight studies (n = 65 720) addressed drug screening accuracy. Among adults, sensitivity and specificity of screening tools for detecting unhealthy drug use ranged from 0.71 to 0.94 and 0.87 to 0.97, respectively. Interventions to reduce drug use were evaluated in 52 trials (n = 15 659) of psychosocial interventions, 7 trials (n = 1109) of opioid agonist therapy, and 13 trials (n = 1718) of naltrexone. Psychosocial interventions were associated with increased likelihood of drug use abstinence (15 trials, n = 3636; relative risk [RR], 1.60 [95% CI, 1.24 to 2.13]; absolute risk difference [ARD], 9% [95% CI, 5% to 15%]) and reduced number of drug use days (19 trials, n = 5085; mean difference, -0.49 day in the last 7 days [95% CI, -0.85 to -0.13]) vs no psychosocial intervention at 3- to 4-month follow-up. In treatment-seeking populations, opioid agonist therapy and naltrexone were associated with decreased risk of drug use relapse (4 trials, n = 567; RR, 0.75 [95% CI, 0.59 to 0.82]; ARD, -35% [95% CI, -67% to -3%] and 12 trials, n = 1599; RR, 0.73 [95% CI, 0.62 to 0.85]; ARD, -18% [95% CI, -26% to -10%], respectively) vs placebo or no medication. While evidence on harms was limited, it indicated no increased risk of serious adverse events. Conclusions and Relevance: Several screening instruments with acceptable sensitivity and specificity are available to screen for drug use, although there is no direct evidence on the benefits or harms of screening. Pharmacotherapy and psychosocial interventions are effective at improving drug use outcomes, but evidence of effectiveness remains primarily derived from trials conducted in treatment-seeking populations.


Assuntos
Programas de Rastreamento/normas , Antagonistas de Entorpecentes/uso terapêutico , Psicoterapia , Detecção do Abuso de Substâncias/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Naloxona/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Guias de Prática Clínica como Assunto , Gravidez , Sensibilidade e Especificidade , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários
6.
JAMA ; 323(22): 2301-2309, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515821

RESUMO

Importance: An estimated 12% of adults 18 years or older and 8% of adolescents aged 12 to 17 years report unhealthy use of prescription or illegal drugs in the US. Objective: To update its 2008 recommendation, the USPSTF commissioned reviews of the evidence on screening by asking questions about drug use and interventions for unhealthy drug use in adults and adolescents. Population: This recommendation statement applies to adults 18 years or older, including pregnant and postpartum persons, and adolescents aged 12 to 17 years in primary care settings. This statement does not apply to adolescents or adults who have a currently diagnosed drug use disorder or are currently undergoing or have been referred for drug use treatment. This statement applies to settings and populations for which services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. Evidence Assessment: In adults, the USPSTF concludes with moderate certainty that screening by asking questions about unhealthy drug use has moderate net benefit when services for accurate diagnosis of unhealthy drug use or drug use disorders, effective treatment, and appropriate care can be offered or referred. In adolescents, because of the lack of evidence, the USPSTF concludes that the benefits and harms of screening for unhealthy drug use are uncertain and that the balance of benefits and harms cannot be determined. Recommendation: The USPSTF recommends screening by asking questions about unhealthy drug use in adults 18 years or older. Screening should be implemented when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. (Screening refers to asking questions about unhealthy drug use, not testing biological specimens.) (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for unhealthy drug use in adolescents. (I statement).


Assuntos
Programas de Rastreamento/normas , Antagonistas de Entorpecentes/uso terapêutico , Psicoterapia , Detecção do Abuso de Substâncias/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Antagonistas de Entorpecentes/efeitos adversos , Sensibilidade e Especificidade , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários
7.
J Sports Sci ; 38(16): 1924-1932, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32543279

RESUMO

Athlete Biological Passport (ABP) is an indirect approach, implemented by WADA, aimed at detecting blood manipulation based on abnormal changes in haematological markers. Cases report the use of hyperhydration as masking method during anti-doping urine sample collection which could potentially mask suspicious fluctuations on ABP profiles. This study investigated the hyperhydration effect on haemoglobin concentration, reticulocyte percentage and OFF-hr score (an algorithm based on haemoglobin concentration and reticulocyte percentage), with and without recombinant human erythropoietin (rHuEPO) administration. A five-week clinical study performed; Baseline and rHuEPO Phase. Water and a sports drink were used as hyperhydration agents. To examine the hyperhydration effect on the normal ABP profile per volunteer, hyperhydration was implemented at 0, 24 and 48 hours during the baseline. During the rHuEPO phase, volunteers received Epoetin beta (3000 IU) with hyperhydration to be implemented at 0, 24 and 48 hours after drug administration. Blood and urine samples were collected and analysed according to WADA guidelines. No significant effect on ABP markers was observed due to hyperhydration at any time during the study. Pre- and post-hyperhydration data were not statistically different compared to individual baseline data. In conclusion, hyperhydration does not affect the ABP haematological markers under the examined conditions.


Assuntos
Biomarcadores/sangue , Doping nos Esportes , Comportamento de Ingestão de Líquido , Hemoglobinas/análise , Contagem de Reticulócitos , Adulto , Biomarcadores/urina , Bebidas Energéticas , Eritropoetina/administração & dosagem , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Fatores de Tempo , Água
8.
J Anal Toxicol ; 44(7): 661-671, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32591782

RESUMO

Oral cannabis products (a.k.a. "edibles") have increased in popularity in recent years. Most prior controlled pharmacokinetic evaluations of cannabis have focused on smoked cannabis and included males who were frequent cannabis users. In this study, 17 healthy adults (8 females), with no cannabis use in at least the past 2 months, completed 4 double-blind outpatient sessions where they consumed cannabis brownies containing Δ9-tetrahydrocannabinol (THC) doses of 0, 10, 25 or 50 mg. Whole blood and oral fluid specimens were collected at baseline and for 8 h post-brownie ingestion. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to measure THC and relevant metabolites. In whole blood, concentrations of THC and 11-hydroxy-THC (11-OH-THC) peaked 1.5-2 h after brownie consumption, decreased steadily thereafter, and typically returned to baseline within 8 h. Blood concentrations for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide were higher than THC and 11-OH-THC and these metabolites were often still detected 8 h post-brownie consumption. Women displayed higher peak concentrations for THC and all metabolites in whole blood compared to men, at least partially owing to their lower body weight/body mass index. Detection of THC in oral fluid was immediate and appeared to reflect the degree of cannabis deposition in the oral cavity, not levels of THC circulating in the blood. THC concentrations were substantially higher in oral fluid than in blood; the opposite trend was observed for THCCOOH. Agreement between ELISA and LC-MS-MS results was high (i.e., over 90%) for blood THCCOOH and oral fluid THC but comparatively low for oral fluid THCCOOH (i.e., 67%). Following oral consumption of cannabis, THC was detected in blood much later, and at far lower peak concentrations, compared to what has been observed with inhaled cannabis. These results are important given the widespread use of toxicological testing to detect recent use of cannabis and/or to identify cannabis intoxication.


Assuntos
Dronabinol/farmacocinética , Psicotrópicos/farmacocinética , Administração Oral , Adulto , Cannabis , Dronabinol/metabolismo , Feminino , Humanos , Masculino , Psicotrópicos/metabolismo , Saliva/metabolismo , Detecção do Abuso de Substâncias/métodos , Adulto Jovem
9.
J Anal Toxicol ; 44(7): 651-660, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32369162

RESUMO

Total urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) concentrations are generally reported following cannabis administration. Few data are available for glucuronide and minor cannabinoid metabolite concentrations. All urine specimens from 11 frequent and 9 occasional cannabis users were analyzed for 11 cannabinoids for ~85 h by liquid chromatography with tandem mass spectrometry following controlled smoked, vaporized or oral 50.6 mg Δ9-tetrahydrocannabinol (THC) in a randomized, placebo-controlled, within-subject dosing design. No cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin (THCV), THC, 11-OH-THC and Δ9-tetrahydrocannabinolic acid were detected in urine. Median THCCOOH-glucuronide maximum concentrations (Cmax) following smoked, vaporized and oral routes were 68.0, 26.7 and 360 µg/L for occasional and 378, 248 and 485 µg/L for frequent users, respectively. Median time to specific gravity-normalized Cmax (Tmax) was 5.1-7.9 h for all routes and all users. Median Cmax for THCCOOH, THC-glucuronide and 11-nor-9-carboxy-Δ9-THCV (THCVCOOH) were <7.5% of THCCOOH-glucuronide Cmax concentrations. Only THC-glucuronide mean Tmax differed between routes and groups, and was often present only in occasional users' first urine void. Multiple THCCOOH-glucuronide and THCCOOH peaks were observed. We also evaluated these urinary data with published models for determining recency of cannabis use. These urinary cannabinoid marker concentrations from occasional and frequent cannabis users following three routes of administration provide a scientific database to assess single urine concentrations in cannabis monitoring programs. New target analytes (CBD, CBN, CBG, THCV and phase II metabolites) were not found in urine. The results are important to officials in drug treatment, workplace and criminal justice drug monitoring programs, as well as policy makers with responsibility for cannabis regulations.


Assuntos
Canabinoides/urina , Glucuronídeos/urina , Detecção do Abuso de Substâncias/métodos , Administração Oral , Adulto , Canabidiol , Canabinol , Cannabis , Humanos , Fumar Maconha , Fumaça
10.
PLoS One ; 15(4): e0232038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324788

RESUMO

BACKGROUND: In the past decade, hundreds of new psychoactive substances (NPS) have been introduced as unclassified alternatives to the illicit drugs. The NPS represent a growing health concern by causing adverse effects and deaths but are usually undetectable by conventional drug tests. This report summarizes results and experiences from analytically confirmed drug-related acute intoxications in emergency departments (ED) and intensive care units (ICU) enrolled in the Swedish STRIDA project on NPS in 2010-2016. METHODS AND FINDINGS: ED/ICU intoxications suspected to involve NPS were enrolled in the project, after initial contact with the Poisons Information Centre (PIC). Serum/plasma and urine samples, and sometimes drug products, were subjected to a comprehensive toxicological investigation, and the PIC retrieved information on associated clinical symptoms and treatment. Between January 2010-February 2016, 2626 cases were enrolled. The patients were aged 8-71 (mean 27, median 24) years and 74% were men. Most biological samples (81%) tested positive for one, or more (70%), psychoactive drugs, including 159 NPS, other novel or uncommon substances, classical recreational and illicit drugs, and prescription medications. When first detected, most NPS or other novel substances (75%) were not banned in Sweden, but they usually disappeared upon classification, which however often took a year or longer. Some NPS were found to be especially harmful and even fatal. CONCLUSIONS: The STRIDA project provided a good overview of the current drug situation in Sweden and demonstrated a widespread use and rapid turnover of many different psychoactive substances. The accomplishment of the project can be attributed to several key factors (close collaboration between the PIC and laboratory to identify suspected poisonings, free analysis, continuous updating of analytical methods, evaluation of adverse effects, and sharing information) that are useful for future activities addressing the NPS problem. The results also illustrated how drug regulations can drive the NPS market.


Assuntos
Psicotrópicos/classificação , Psicotrópicos/envenenamento , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Idoso , Criança , Serviço Hospitalar de Emergência , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Psicotrópicos/isolamento & purificação , Suécia , Adulto Jovem
11.
Sud Med Ekspert ; 63(2): 32-40, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32297497

RESUMO

Aim of this study was to develop a fast screening method for identification of illegal drugs including new psychoactive substances and their metabolites in human urine by means of liquid chromatography mass-spectrometry HPLC-MS/MS screening method for identification of 138 psychoactive substances in urine was established, validated and tested. High-resolution mass-spectrometry was used for confirmation of the developed approach. The developed method was tested on 50 positive urine samples containing the target compounds, which proved reliability and accuracy of the established screening method.


Assuntos
Cromatografia Líquida de Alta Pressão , Drogas Ilícitas/urina , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem , Humanos , Reprodutibilidade dos Testes
12.
J Anal Toxicol ; 44(5): 461-469, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32020169

RESUMO

5-Methoxy-N,N-Diisopropyltryptamine (5-MeO-DIPT) is a designer hallucinogen derived from tryptamine and its use has been banned by many countries. In this study, a qualitative and quantitative method was developed for determining 5-MeO-DIPT in urine by gas chromatography high-resolution mass spectrometry. 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO-IPT) were identified as 5-MeO-DIPT metabolites in abusers' urine. 5-MeO-DIPT was extracted from urine by liquid-liquid extraction with ethyl acetate under alkaline conditions. The extract was analyzed by GC-Orbitrap-MS in full scan mode with a resolution of 60,000 full width at half maxima (FWHM). The linear range of this method was 2-300 ng/mL with r > 0.99, and the limit of detection was 1 ng/mL. The accuracy and precision were 93-108.7% and 3.1-10.3%, respectively. This method is simple and sensitive. It has been successfully used to detect 5-MeO-DIPT in drug abusers' urine, which showed that the concentrations of 5-MeO-DIPT were between 1 and 2.8 ng/mL. 5-OH-DIPT and 5-MeO-IPT, two urinary major metabolites of 5-MeO-DIPT, were identified in urine samples from 5-MeO-DIPT users. Furthermore, the stability of 5-MeO-DIPT in human urine was investigated. It was discovered that the concentration of 5-MeO-DIPT in urine decreased by 22.8, 33.2 and 38.2% after samples were stored for 24 h at 25°C, 5 days at 4°C and 7 days at 4°C, respectively. And 5-MeO-DIPT in urine were stable after they were stored for 30 days at -20°C. Therefore, it is recommended that urine should be stored under freezing conditions before performing 5-MeO-DIPT analysis.


Assuntos
5-Metoxitriptamina/análogos & derivados , Detecção do Abuso de Substâncias/métodos , 5-Metoxitriptamina/urina , Drogas Desenhadas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectrometria de Massas , Serotonina/análogos & derivados
13.
J Anal Toxicol ; 44(5): 490-498, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32020176

RESUMO

Recently, an increased tendency to use various metals has been observed in the sports competition fields. Many of these metals and their organic complexes reportedly have good pharmacologic, therapeutic and performance-enhancement uses; they are banned or recommended as controlled medications in competitive sports. The objective of this research was to determine the concentration of pharmacologically relevant metals in urine samples collected from racehorses at various sport events, develop a method and assess the concentrations of above metals using inductively coupled plasma mass spectrometry (ICP-MS). Seven alkali-alkaline earth metals (lithium, sodium, potassium, magnesium, calcium, strontium and barium) and six heavy metals (chromium, cobalt, copper, zinc, arsenic and selenium) were studied in detail. To compare and confirm the concentrations of these metals, the screening was carried out on the basis of region and sex of the animal. ICP-MS provides extremely high sensitivity that enables the determination of the metals at very low concentration from complex biological matrices. From the research, it is clear that irrespective of sex and region the concentration of metal is very high in some samples, might be accidental or intentional doping to improve sporting performances. This research work is of significant importance in setting threshold values for screening metals in race day samples in order to avoid potential harmful effects on athletes and the depth of malpractices, it can bring to sports.


Assuntos
Doping nos Esportes , Cavalos/metabolismo , Metais/urina , Substâncias para Melhoria do Desempenho/urina , Detecção do Abuso de Substâncias/métodos , Oligoelementos/urina , Animais , Arsênico , Cromo , Cobalto , Substâncias para Melhoria do Desempenho/sangue , Potássio , Selênio , Sódio , Espectrofotometria Atômica , Oligoelementos/sangue
14.
J Anal Toxicol ; 44(5): 422-439, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32020178

RESUMO

Systematic toxicological approaches that employ both ideology changes and improvements in instrumentation and sample extraction allow for improved toxicology testing efficiency through lower sensitivities, higher specificity and minimized resource use. Historically, the San Francisco Office of the Chief Medical Examiner relied heavily on a gas chromatography mass spectrometry (GC-MS) testing regime, comprised of individual drug-class confirmation and quantitation assays. Traditional methods utilizing GC-MS typically require iterations of testing, exhausting sample volume, and hindering productivity and turnaround times, particularly for polypharmacy cases frequently seen in modern postmortem toxicology. The method described here consolidated the scope of seven legacy methods into a single liquid chromatography tandem mass spectrometry (LC-MS/MS) method for better sensitivity, higher throughput, minimal sample consumption for the quantitation of drugs of abuse and improved quality assurance with the incorporation of smart, automated processing. About 100 µL of blood or urine were rapidly extracted using a simple acetonitrile protein crash and subsequent in-vial filtration and injected on to an LC-MS-MS system. The developed method was fully validated to SWGTOX and international guidelines and incorporated 55 analytes along with a customized query that facilitates rapid and consistent application of acceptability criteria for data processing and review. Applicability was demonstrated with the analysis of 1,389 samples (858 blood and 531 urine) where at least 41% of positive results may have been missed due to their decreased sensitivity and 11% of results were not within the scope of the previous analytical methods estimated. On average, cases in this study would have previously required three distinct GC-MS assays, 3 mL of blood, and upwards of 30 h of active staff time. The described LC-MS-MS analytical approach has mitigated the need to perform multiple assays, utilized only 0.1 mL of sample, significantly reduced analyst work time, incorporated 10 additional analytes and allowed for a more comprehensive testing regime to better inform cause of death determinations.


Assuntos
Toxicologia Forense/métodos , Detecção do Abuso de Substâncias/métodos , Autopsia , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectrometria de Massas em Tandem
15.
J Anal Toxicol ; 44(5): 482-489, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32020179

RESUMO

This study presents a retrospective analysis of the prevalence of drug abuse in Shanghai by hair analysis. Files and toxicology analysis results of a total of 5,610 cases requesting for hair analysis of abused drugs at the Academy of Forensic Science (AFS) in Shanghai over 12 months between August 2018 and July 2019 were reviewed. All cases of drug abuse identified by hair analysis were from the public security organs in Shanghai, China. Hair samples were analyzed for drugs of abuse and related metabolites, mainly including amphetamine (AMP), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), tetrahydrocannabinol (THC), ketamine (K), norketamine (NK), cocaine (COC), benzoylecgonine, morphine, 6-acetylmorphine, flunitrazepam, and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Among the 5,610 cases, 1,713 (30.5%) were positive for drugs of abuse, with amphetamine-type stimulants (ATS) (57%), including amphetamines (AMP and MA) (48%), MDMA and MDA (9%), being the most frequently detected drugs, followed by THC (14%), COC (8%), 5-MeO-DIPT (8%), and K (7%). The majority (75%) of positive hair samples were from male subjects. Overall, 77% of abusers were younger than 44 years old. The proportion of female subjects (22.3%) under 24 years was larger than that of male subjects (7.8%). There were 132 cases (7.7%) in which more than one type of drug was detected among 1,713 drug-positive cases. The most common combination was MDMA and K. The present study characterizes the current toxicological profile of drug abuse cases and provides a scientific basis for drug abuse prevention. Moreover, the hair concentration distributions of the commonly abused drugs in positive cases have been reported.


Assuntos
Análise do Cabelo , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , 3,4-Metilenodioxianfetamina , Adulto , Anfetaminas , Estimulantes do Sistema Nervoso Central , China/epidemiologia , Cromatografia Líquida , Cocaína/análogos & derivados , Feminino , Cabelo/química , Humanos , Drogas Ilícitas , Masculino , Metanfetamina , Derivados da Morfina , N-Metil-3,4-Metilenodioxianfetamina , Prevalência , Estudos Retrospectivos , Espectrometria de Massas em Tandem
16.
Clin Chem ; 66(2): 324-332, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040576

RESUMO

BACKGROUND: Rapid identification of fentanyl at the point-of-care is critical. Urine fentanyl concentrations in overdose cases start at single-digit nanograms per milliliter. No fentanyl point-of-care assay with a cutoff at single-digit nanograms per milliliter is available. METHODS: A competitive lateral flow assay (LFA) was developed using gold nanoparticles and optimized for rapid screening of fentanyl in 5 minutes. Urine samples from 2 cohorts of emergency department (ED) patients were tested using the LFA and LC-MS/MS. The 2 cohorts consisted of 218 consecutive ED patients with urine drug-of-abuse screen orders and 7 ED patients with clinically suspected fentanyl overdose, respectively. RESULTS: The LFA detected fentanyl (≥1 ng/mL) and the major metabolite norfentanyl (≥10 ng/mL) with high precision. There was no cross-reactivity with amphetamine, cocaine, morphine, tetrahydrocannabinol, methadone, buprenorphine, naloxone, and acetaminophen at 1000 ng/mL and 0.03%, 0.4%, and 0.05% cross-reactivity with carfentanil, risperidone, and 9-hydroxyrisperidone, respectively. In 218 consecutive ED patients, the prevalence of cases with fentanyl ≥1 ng/mL or norfentanyl ≥10 ng/mL was 5.5%. The clinical sensitivity and specificity of the LFA were 100% (95% CI, 75.8-100%) and 99.5% (95% CI, 97.3-99.9%), respectively. The positive and negative predictive values were 92.3% (95% CI, 66.7-98.6%) and 100% (95% CI, 98.2-100%), respectively. The concordance between the LFA and LC-MS/MS was 100% in the 7 suspected fentanyl overdose cases (5 positive, 2 negative). CONCLUSIONS: The LFA can detect fentanyl and norfentanyl with high clinical sensitivity and specificity in the ED population with rapid fentanyl screening needs.


Assuntos
Overdose de Drogas/diagnóstico , Fentanila/análise , Detecção do Abuso de Substâncias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/urina , Bioensaio , Cromatografia Líquida/métodos , Overdose de Drogas/urina , Serviço Hospitalar de Emergência , Feminino , Fentanila/análogos & derivados , Fentanila/urina , Ouro , Humanos , Imunoensaio/métodos , Masculino , Nanopartículas Metálicas , Pessoa de Meia-Idade , Testes Imediatos , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Urinálise/métodos
17.
J Anal Toxicol ; 44(6): 618-622, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32020184

RESUMO

Carfentanil is a synthetic opioid approximately 10,000 times as powerful as morphine. It is not approved for human use. However, cases of death associated with carfentanil have become more frequent in recent years. In this report, the case of a patient with a positive urine test for norcarfentanil (a metabolite of carfentanil) is described. The analytical method leading to the detection is summarized. This is a rarely reported case of survival of carfentanil use. It is unique in the published literature of an account of a norcarfentanil-positive patient concurrently enrolled in a substance use disorder treatment program. To the authors' knowledge, this is the first documented case of a carfentanil exposure in the state of New York.


Assuntos
Analgésicos Opioides/metabolismo , Fentanila/análogos & derivados , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias , Fentanila/metabolismo , Humanos , Masculino
18.
J Anal Toxicol ; 44(6): 580-588, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32064503

RESUMO

An LC-MS-MS method for the determination of 14 benzodiazepines (BZDs) (alprazolam, α-hydroxyalprazolam, clonazepam, bromazepam, diazepam, nordiazepam, lorazepam, lormetazepam, oxazepam, flunitrazepam, 7-aminoflunitrazepam, triazolam, midazolam and zolpidem) and 15 antidepressants (ADs) (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, norclomipramine, fluoxetine, norfluoxetine, sertraline, norsertraline, paroxetine, venlafaxine, desmethylvenlafaxine, citalopram and desmethylcitalopram) in meconium was developed and validated. Meconium samples (0.25 ± 0.02 g) were homogenized in methanol and subjected to mixed-mode cation exchange solid-phase extraction. Chromatographic separation was performed in reversed phase, with a gradient of 0.1% formic acid in 2 mM ammonium formate and acetonitrile. Two different chromatographic gradient methods were employed, one for the separation of ADs and another for BZDs. Analytes were monitored by tandem mass spectrometry employing electrospray positive mode in MRM mode (2 transitions per compound). Method validation included: linearity [n = 5, limit of quantification (LOQ) to 400 ng/g], limits of detection (n = 6, 1-20 ng/g), LOQ (n = 9, 5-20 ng/g), selectivity (no endogenous or exogenous interferences), accuracy (n = 15, 90.6-111.5%), imprecision (n = 15, 0-14.6%), matrix effect (n = 10, -73 to 194.9%), extraction efficiency (n = 6, 35.9-91.2%), process efficiency (n = 6, 20.1-188.2%), stability 72 h in the autosampler (n = 3, -8.5 to 9%) and freeze/thaw stability (n = 3, -1.2 to -47%). The method was applied to four meconium specimens, which were analyzed with and without hydrolysis (enzymatic and alkaline). The authentic meconium samples tested positive for alprazolam, α-hydroxyalprazolam, clonazepam, diazepam, nordiazepam, fluoxetine, norfluoxetine, clomipramine and norclomipramine. Therefore, the present LC-MS-MS method allows a high throughput determination of the most common BZDs and ADs in meconium, which could be useful in clinical and forensic settings.


Assuntos
Antidepressivos/análise , Benzodiazepinas/análise , Toxicologia Forense , Mecônio/química , Detecção do Abuso de Substâncias/métodos , Alprazolam/análogos & derivados , Cromatografia Líquida , Clonazepam , Humanos , Limite de Detecção , Nordazepam , Oxazepam , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Cloridrato de Venlafaxina , Zolpidem
19.
J Anal Toxicol ; 44(6): 521-530, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32091095

RESUMO

The synthetic opioid landscape continues to change as non-fentanyl-related substances appear in forensic toxicology casework. Among the newest synthetic opioids to emerge is isotonitazene, an analogue of a benzimidazole class of analgesic compounds. Isotonitazene is an active and potent synthetic opioid, but the extent to which this compound is causing toxicity among drug users was previously unknown. This report describes the confirmation and quantitation of isotonitazene in blood, urine and vitreous fluid through standard addition, as well as in vivo metabolic profile determination in drug users. Quantitative analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS), and metabolite discovery was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In total, 18 cases were confirmed positive for isotonitazene, nine of which were previously negative for any opioid. The average isotonitazene concentration in blood was 2.2 ± 2.1 ng/mL (median 1.75 ng/mL, range 0.4-9.5 ng/mL), and the average isotonitazene concentration in urine was 2.4 ± 1.4 ng/mL (median 2.7 ng/mL, range 0.6-4.0 ng/mL). The lowest concentration of isotonitazene in blood was 0.4 ng/mL (two cases) with no other opioids present; findings in death investigations. Four metabolites of isotonitazene were detected in vivo. N- and O-dealkylation products were determined to be the most prominent urinary biomarkers, while 5-amino-isotonitazene was identified in most blood samples. The prevalence and popularity of isotonitazene continue to increase in the United States in early 2020. Toxicologists, medical examiners and coroners should be aware of novel opioids outside the standard scope of testing, especially in medicolegal death investigations. Forensic scientists should add isotonitazene to testing procedures, and public health officials should counsel about potent new drugs and the dangers of opioid use.


Assuntos
Analgésicos Opioides/análise , Benzimidazóis/análise , Drogas Desenhadas/análise , Toxicologia Forense , Detecção do Abuso de Substâncias/métodos , Drogas Ilícitas
20.
J Anal Toxicol ; 44(6): 623-626, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32091106

RESUMO

A 48-year-old nurse with an alcohol use disorder history was being monitored in a professional health program. She consistently produced low-to-moderate urinary ethyl sulfate (EtS) concentrations in the absence of detectable urinary ethyl glucuronide (EtG), blood phosphatidylethanol and breath alcohol. She denied intentional ethanol consumption. After prolonged monitoring in a drug treatment program, including a period in a controlled environment, we concluded that this individual's urinary EtS likely resulted from anatomical and microbial factors related to Roux-en-Y gastric bypass surgery, with possible contributions from hidden dietary sources of ethanol. We have no definitive explanation for the lack of urinary EtG.


Assuntos
Alcoolismo/urina , Glucuronatos/urina , Detecção do Abuso de Substâncias/métodos , Ésteres do Ácido Sulfúrico/urina , Consumo de Bebidas Alcoólicas/urina , Feminino , Glicerofosfolipídeos/sangue , Humanos , Pessoa de Meia-Idade
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