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1.
Forensic Sci Int ; 307: 110136, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31896021

RESUMO

In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography-tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %-95 %; that of diazepam, paroxetine and triazolam was 10 %-45 %; and that of brotizolam, etizolam and levomepromazine was 1 %-5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.


Assuntos
Estabilidade de Medicamentos , Toxicologia Forense/métodos , Fígado/química , Psicotrópicos/análise , Psicotrópicos/química , Animais , Cromatografia Líquida , Fixadores , Formaldeído , Preservação de Órgãos , Manejo de Espécimes , Suínos , Espectrometria de Massas em Tandem
2.
Forensic Sci Int ; 307: 110137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31927248

RESUMO

Seizures of synthetic opioids have increased since 2012, with a 45 % increase in synthetic opioid related deaths between 2016 and 2017 in US. Recently, concerns have arisen around these substances and their illicit use also in several European countries. Our aim was to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of 16 synthetic opioids in segmented hair, including fentanyl, norfentanyl, acetylfentanyl, U-47700, AH-7921, acrylfentanyl, crotonylfentanyl, butyrylfentanyl, methoxacetylfentanyl, U-49900, valeryfentanyl, 4-fluoro-iso-butyrylfentanyl, ocfentanyl, furanylfentanyl, tetrahydrofuranylfentanyl, and alfetanyl. Sample preparation involved washing the hair in dichloromethane, water and methanol, and extraction in methanol, followed by solid phase extraction clean-up. This method was validated for linearity, limit of quantification (LLOQ), precision and bias, selectivity, stability, matrix effects, extraction efficiency of the clean up procedure, and carryover. LLOQs ranged from 0.15-1pg/mg, and the calibration ranged from the LLOQ up to 500pg/mg. Intra and inter-day precision were evaluated at low and high concentrations, with spiked QCs, during 8 days and the results were satisfactory with RSD<15 % for all the compounds except for norfentanyl (22 %) and alfentanyl (19 %). Two external certified QCs containing fentanyl at 11 and 105pg/mg were also analysed within each batch and the RSD and bias were lower than 16 % and 10 %, respectively. Matrix effects compensated by internal standard fentanyl-d5 (MEIS), were between 77-115 % (RSD<10 %) and extraction efficiency of the clean-up procedure was between 66-93 % (RSD<21 %). Processed sample stability and carryover were acceptable for all of the compounds. The method was applied to 17 authentic hair samples (body or head hair) from US fentanyl analogue users. When head hair was available, the hair strands were analysed in 1cm/segment. Concentrations ranges were as follows: fentanyl (n=16) 2->ULOQ (500) pg/mg, norfentanyl (n=14) 1-38pg/mg, acetylfentanyl (n=7) 0.6->ULOQ (250) pg/mg, furanylfentanyl (n=5) 2-123pg/mg, tetrahydrofuranylfentanyl (n=1) 0.5-63pg/mg and valerylfentanyl (n=1) 2.1->ULOQ (50) pg/mg, along the hair strands. To our knowledge, this is the first time where concentrations of tetrahydrofuranylfentanyl, and valerylfentanyl in hair are reported. The same samples were also analysed for the determination of other drugs of abuse using our routine method (also in 1cm/segment for head hair when available). The results demonstrated poly-drug use in these fentanyl-analogue users population (mean drugs: n=5): amphetamine and/or methamphetamine (n=10), buprenorphine (n=5), cocaine (n=8), methadone (n=8), 6-MAM (n=17), meperidine (n=1), oxycodone (n=11), tramadol (n=3). Evaluation of the concentrations of these drugs, together with the fentanyl analogues is discussed in the present paper. Two authentic samples from two Belgian post-mortem cases, were also analysed showing fentanyl use and in one case polydrug use. The results demonstrated multi-analyte quantitative methods, including fentanyl analogues, are becoming useful in forensic laboratories involved in hair analysis, and in particular when polydrug use is suspected.


Assuntos
Analgésicos Opioides/análise , Fentanila/análogos & derivados , Fentanila/análise , Cabelo/química , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida de Alta Pressão/métodos , Toxicologia Forense/métodos , Humanos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Medicamentos Sintéticos/análise , Espectrometria de Massas em Tandem/métodos
3.
Forensic Sci Int ; 306: 110071, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785510

RESUMO

The presence of Ethyl glucuronide (EtG) in hair provides a strong indication of ethanol consumption and its investigation is of interest in both clinical and forensic contexts because of the wide window of detection. However, due to the possibility of false negative results in cases of small ethanol intake or excessive hair washing, the combined measurement of ethyl palmitate (EtP) with EtG could be useful. In this study, a sensitive UHPLC-MS/MS procedure for the measurement of EtG in hair was developed and validated, using optimized sample preparation and chromatographic separation. Milled hair was extracted with water for 24 h at room temperature, followed by clean-up of the extract by ion-exchange solid phase extraction (SPE). Extraction was highly efficient, with yield of 96.93-101.06%. Chromatographic separation was performed with a Fluoro-Phenyl stationary phase. The assay was linear from 4 to 500pgmg-1, with accuracy in the range of 100.30-106.16%. Matrix effects (-0.87 to 5.89%) were adequately compensated by the use of deuterated EtG as internal standard. EtG was measured in hair samples of 46 volunteers, and results were compared with hair concentrations of ethyl palmitate (EtP) and the score in the AUDITC questionnaire. EtG hair concentrations were significantly correlated to the AUDIT-C classification (rs=0.365, p<0.05), but not to EtP hair levels. The diagnostic performance of EtG hair concentrations to identify excessive or moderate ethanol use was similar to the capability of AUDIT-C to identify severe and high health risk (Kappa, p=0.013). The developed assay is suitable for clinical use, providing a useful tool to evaluate chronic ethanol consumption.


Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo/diagnóstico , Glucuronatos/análise , Cabelo/química , Detecção do Abuso de Substâncias/métodos , Adulto , Biomarcadores/análise , Cromatografia Líquida , Feminino , Toxicologia Forense/métodos , Humanos , Masculino , Ácidos Palmíticos/análise , Extração em Fase Sólida , Espectrometria de Massas em Tandem
4.
Forensic Sci Int ; 306: 110074, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809905

RESUMO

In forensic investigations, such as drug-facilitated crimes, reference values are useful for interpretation of hair results. The aim of this study was to establish levels of zopiclone and two main metabolites, N-desmethylzopiclone and zopiclone N-oxide, in hair after the administration of a single dose of zopiclone, as very limited data are published. A controlled study was performed, where 16 volunteers consumed either 5 or 10mg zopiclone. Hair was sampled prior to consumption and 14, 30, 60, and 120 days after intake. The deposition of drug in hair segments of all sampling time points was followed in small hair segments of 5-mm, using a validated ultra-high performance liquid chromatography-tandem mass spectrometry method. In all participants, hair segments corresponding to the time of intake were positive for zopiclone, but also with lower concentrations in the neighbouring segments. The highest zopiclone concentrations were detected in samples collected 30 or 60 days after intake. For all sampling time points maximum values for the 5-mg dose ranged from 5.0-370pg/mg for zopiclone and 5.4 to 300pg/mg for N-desmethylzopiclone, where the maximum values for the 10-mg dose ranged from 17 to 590pg/mg for zopiclone and 25-410pg/mg for N-desmethylzopiclone for all sampling time points. No significant difference in concentrations was found between the two dosing groups for either zopiclone or N-desmethylzopiclone. Almost half of the participants showed lower levels 14 days after intake than in the later sampling time points. The metabolite to parent drug ratio of N-desmethylzopiclone to zopiclone varied from 0.6 to 3.4 (median=1.2) for the maximum levels of all sampling time points. N-desmethylzopiclone are suggested to serve as an additional marker to confirm the intake of zopiclone. Traces of zopiclone N-oxide were detected in hair from only eight participants. This study showed, that it was possible to follow zopiclone and N-desmethylzopiclone in hair for 4 months even though the drugs was divided into several segments in the latest collected hair samples, and no obvious wash-out effect between the sampling time points by e.g. personal hygiene could be discerned because the cumulated amount at each sampling time point was similar. We conclude that the analysis of short segments e.g. segments of 5-mm can help determine the time of a single intake of zopiclone and that obtaining a sample 1-2 months after a drug exposure provide the best conditions to detect and interpret the results.


Assuntos
Compostos Azabicíclicos/análise , Cabelo/química , Hipnóticos e Sedativos/análise , Piperazinas/análise , Adulto , Compostos Azabicíclicos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Feminino , Toxicologia Forense , Cor de Cabelo , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Piperazinas/administração & dosagem , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem
5.
J Forensic Sci ; 65(1): 183-188, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31430392

RESUMO

2,4-dinitrophenol (2,4-DNP) is a compound used in the early 1900s as a weight-loss drug but later prohibited due to its severe adverse effects, including death. It has however been attracting interest, due to its weight-loss properties, and appears to be re-emerging in forensic casework. As 2,4-DNP is available for use in industry and as a pesticide and easily accessible online, the dissemination of this drug can be fast. The compound exerts its effects through inhibition of ATP synthesis, and corresponding thermogenic energy loss which can be fatal. A method for qualitative and quantitative analysis of 2,4-DNP in blood and urine specimens using GC-MS with hydrogen as carrier gas is described. The method was validated and displayed acceptable performance parameters with linearity (R2 higher than 0.998), inter-assay imprecision (lower than 10.6%), intra-assay imprecision (lower than 10.7%), and extraction efficiency (92.1%). Stability of 2,4-DNP in blood and urine was studied, and the drug was stable up to 30 days refrigeration or frozen. Six cases in United States suspected to be related to 2,4-DNP were analyzed. Three cases were found to be positive for 2,4-DNP. Concentrations of 2,4-DNP were in the range of 61.6-220 mg/L in urine and <3-114 mg/L in blood. Based on our findings, we suggest that medical examiners and forensic toxicologists be aware of the reappearance of 2,4-DNP, including this compound as a target in death investigations related to weight-loss drugs.


Assuntos
2,4-Dinitrofenol/sangue , 2,4-Dinitrofenol/urina , Fármacos Antiobesidade/sangue , Fármacos Antiobesidade/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , 2,4-Dinitrofenol/efeitos adversos , Fármacos Antiobesidade/efeitos adversos , Estabilidade de Medicamentos , Feminino , Toxicologia Forense , Humanos , Masculino , Manejo de Espécimes , Estados Unidos , Adulto Jovem
6.
J Forensic Sci ; 65(1): 52-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31433500

RESUMO

Mitragyna speciosa (MS), a plant commonly known as kratom, is a widely used "legal high" opiate alternative for pain relief. DNA extracted from MS and 26 additional plant species was amplified by PCR using primers targeting the strictosidine beta-D-glucosidase (SGD) and secologanin synthase 2 (SLS2) genes and detected by high-resolution melt curves using three intercalating dyes. Amplicon sizes were confirmed using agarose gel electrophoresis. The observed melt temperatures for SGD and SLS2 were 77.08 ± 0.38°C and 77.61 ± 0.46°C, respectively, using SYBR® Green I; 80.18 ± 0.27°C and 80.59 ± 0.08°C, respectively, using Radiant™ Green; and 82.19 ± 0.04°C and 82.62 ± 0.13°C, respectively, using the LCGreen® PLUS dye. The SLS2 primers demonstrated higher specificity and identified MS DNA at 0.05 ng/µL. In a duplex reaction, SLS2 and tetrahydrocannabinoic acid synthase gene primers detected and differentiated MS and Cannabis sativa (CS) by melt peaks at 82.63 ± 0.35°C and 85.58 ± 0.23°C, respectively, using LCGreen® PLUS.


Assuntos
Cannabis/genética , DNA de Plantas/genética , Toxicologia Forense/métodos , Mitragyna/genética , Primers do DNA , Eletroforese em Gel de Ágar , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Temperatura de Transição
7.
Forensic Sci Int ; 306: 110064, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786513

RESUMO

Hemp seeds and hempseed oil are marketed on- and off-line as health foods and cosmetics and have been reported to have high nutrient contents. However, because of the various side effects of cannabinoids, especially △9-tetrahydrocannabinol (THC), many countries regulate upper limits for THC in products, which creates the need for analytical techniques capable of measuring THC, cannabidiol (CBD), and cannabinol (CBN) levels in commercial hemp seeds and hempseed oil. In the present study, hemp seed and hempseed oil extracts obtained by methanol extraction, were analyzed by gas chromatography-mass spectrometry (GC/MS). Validation of the technique used was performed using calibration curves and by determining LODs, LOQs, specificities, selectivities, and intra- and inter-day precision and accuracies. In addition, matrix effects, process efficiencies, recoveries, and sample stabilities were investigated. In hemp seeds, as determined using the fully optimized method THC concentrations ranged from 0.06 to 5.91 µg/g, CBD concentrations from 0.32 to 25.55 µg/g, and CBN concentrations from 0.01 to 1.50 µg/g; CBN/THC ratios ranged from 0.1 to 1.60, and CBD/THC ratios from 0.11 to 62.56. Furthermore, the (THC + CBN)/CBD ratio of most hemp seed samples was less than one. In hempseed oil, THC concentrations ranged from 0.3 to 19.73 µg/mL, CBD concentrations from 6.66 to 63.40 µg/mL, CBN concentrations from 0.11 to 2.31 µg/mL, CBN/THC ratios from 0.12 to 0.42, and CBD/THC ratios from 3.21 to 22.50. Furthermore, (THC + CBN)/CBD ratios in all hempseed oil samples were less than one. The optimized methanol extraction-GC/MS technique was found to be satisfactory for determining THC, CBD, and CBN concentrations in hemp seeds and hempseed oil.


Assuntos
Canabinoides/análise , Cannabis/química , Comércio , Óleos Vegetais/química , Sementes/química , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , República da Coreia
8.
Forensic Sci Int ; 306: 110058, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786516

RESUMO

Hair is one of the key samples for judging drug abuse in the field of forensic science. However, few studies have examined synthetic cannabinoids and their metabolites in human hair. Synthetic cannabinoids are a class of chemicals that bind to cannabinoid receptors, but they differ structurally from the cannabinoids found in cannabis. They have been sold sprayed on dried, shredded plant material under brand names such as "Spice" since the 2000s. In South Korea, synthetic cannabinoids have been widely distributed since 2009 and many types detected up to now. Unlike traditional drugs such as methamphetamine and cannabis, the abuse trends of synthetic cannabinoids were variable by regions and changed according to the times. If new types of synthetic cannabinoids become popular which has been altered in some structures, it becomes difficult to identify using exist analytical method. Therefore, it is important to develop a new analytical method for synthetic cannabinoids currently being abused in society. In this study, we developed simultaneous analytical methods for the detection of 18 synthetic cannabinoids and 41 of their metabolites in authentic human hair samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selectivity, linearity, limits of detection (LODs), limits of quantification (LOQs), precision, accuracy, matrix effect, recovery, and process efficiency were evaluated, and all results were acceptable. Additionally, the distribution of synthetic cannabinoids in the head hair of Korean drug abusers from 2016 to 2018 was investigated. Hair samples from 43 individuals suspected of synthetic cannabinoid use were provided by law enforcement agencies. The drugs detected most prevalently in the head hair of Korean drug abusers were AB-CHMINACA and JWH-210.


Assuntos
Canabinoides/análise , Cabelo/química , Detecção do Abuso de Substâncias/métodos , Medicamentos Sintéticos/análise , Adulto , Cromatografia Líquida , Feminino , Toxicologia Forense , Humanos , Limite de Detecção , Masculino , República da Coreia , Espectrometria de Massas em Tandem , Adulto Jovem
9.
Forensic Sci Int ; 306: 110070, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786517

RESUMO

Propofol abuse has been reported worldwide, suggesting the need to establish analytical methods for human biological samples to investigate the abuse of propofol. This study aimed to investigate the relationship between dose and hair concentration using a simple and rapid analytical method developed and validated in this study. In the sample preparation, hair samples were washed with distilled water and methanol and extracted in methanol during 16h at room temperature. After centrifugation and evaporation, the residue was reconstituted and filtered through a 0.22µm membrane filter before LC-MS/MS analysis. The precursor-to-product ion transitions were 353 → 175, 113 for propofol glucuronide and m/z 370 → 175, 113 for internal standard(propofol glucuronide-d17). The calibration curves were satisfactory (R2=0.9997) and the limits of detection and quantification were 2 and 5pg/mg, respectively. In addition, this study collected the history of propofol use from subjects using a questionnaire and analyzed subjects' hair samples using a validated analytical method. As a result, the concentrations of propofol glucuronide ranged from 7 to 122pg/mg (mean : 51pg/mg). There were cases of positive relationships, but generally there was no correlation between dose and hair concentration.


Assuntos
Glucuronídeos/análise , Cabelo/química , Hipnóticos e Sedativos/análise , Propofol/análise , Detecção do Abuso de Substâncias/métodos , Adulto , Cromatografia Líquida , Feminino , Toxicologia Forense , Glucuronídeos/administração & dosagem , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Espectrometria de Massas em Tandem , Adulto Jovem
10.
J Forensic Sci ; 65(1): 61-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31310334

RESUMO

Unregulated cacti from the genus Echinopsis are used recreationally as mescaline-containing alternatives to the outlawed peyote. Echinopsis-derived plant materials appear in a variety of nondescript forms, making rapid assessment of whether they are mescaline-containing materials or simply innocuous plant-derived food products, very challenging. Reported here is a DART-HRMS approach for the rapid detection of mescaline in whole plant material and a validated method for the quantification of mescaline in cactus tissue, using mescaline-d9 as the internal standard. Calibration curves exhibited R2 values of ≥0.995, and the method exhibited a LLOQ and a linear range of 1 ppm and 1-100 ppm, respectively. Application of the method to commercially available Echinopsis spp. yielded results consistent with previous studies performed by GC- and LC-MS, with mescaline levels of <2% dry weight in all cases. Therefore, DART-HRMS is a suitable technique for the rapid screening of mescaline and its subsequent quantification within complex plant-derived matrices.


Assuntos
Cactaceae/química , Alucinógenos/análise , Espectrometria de Massas/métodos , Mescalina/análise , Toxicologia Forense , Humanos , Transtornos Relacionados ao Uso de Substâncias
11.
J Forensic Sci ; 65(1): 170-182, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31211877

RESUMO

Forty-three fatalities involving the potent synthetic cannabinoid, 5-Fluoro-ADB, are summarized. For each case, a description of the terminal event, autopsy findings, cause of death, qualitative identification of 5-Fluoro-ADB and its ester hydrolysis metabolite, 5-Fluoro-ADB metabolite 7, in urine, and the quantitative values obtained in the blood specimens are outlined. Central blood concentrations ranged from 0.010 to 2.2 ng/mL for 5-Fluoro-ADB and 2.0 to 166 ng/mL for 5-Fluoro-ADB metabolite 7. Peripheral blood concentrations ranged from 0.010 to 0.77 ng/mL and 2.0 to 110 ng/mL for 5-Fluoro-ADB and 5-Fluoro-ADB metabolite 7, respectively. The majority of cases resulted in central to peripheral blood concentration ratios greater than 1 for 5-Fluoro-ADB (58%) and 5-Fluoro-ADB metabolite 7 (71%) suggesting that postmortem redistribution occurs to some extent. Combining the increased cardiac weight and/or gastric volume and toxicology data identifying 5-Fluoro-ADB, it is hypothesized that abuse of this substance may precipitate a dysrhythmia and cause sudden death.


Assuntos
/sangue , Indazóis/sangue , Indazóis/urina , Abuso de Maconha/mortalidade , Adulto , Cromatografia Gasosa , Cromatografia Líquida , Técnica de Imunoensaio Enzimático de Multiplicação , Ensaio de Imunoadsorção Enzimática , Toxicologia Forense , Humanos , Indazóis/efeitos adversos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estrutura Molecular , Miocárdio/patologia , Tamanho do Órgão , Estômago/patologia
12.
J Forensic Sci ; 65(1): 288-294, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31454427

RESUMO

Lacosamide is a functionalized amino acid with antiepileptic function. Therapeutic drug monitoring (TDM) in patients for lacosamide is critical as it allows clinicians to control epileptic seizures. A single liquid-liquid extraction step was applied for the extraction of lacosamide from whole blood samples which were thereafter analyzed by GC-MS. Optimum extraction conditions were selected on the basis of experiments with various solvents at different pHs, indicating ethyl acetate at pH 12 as the most efficient parameters for the extraction of lacosamide. Method exhibited linearity from 2 to 100 µg/mL with R2  = 0.998. Accuracy and precision were evaluated at three concentrations and found to be within acceptable limits. LOD and LOQ were determined at 0.1 and 0.5 µg/mL, respectively. Lacosamide was found to be stable at storage conditions. The developed method was applied successfully in clinical samples and postmortem blood sample from an overdose case.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Gasosa-Espectrometria de Massas , Lacosamida/sangue , Anticonvulsivantes/envenenamento , Monitoramento de Medicamentos , Toxicologia Forense , Humanos , Lacosamida/envenenamento , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Envenenamento/diagnóstico
13.
Forensic Sci Int ; 306: 110094, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31864115

RESUMO

Methamphetamine (MAMP) is one of the most commonly abused illicit drugs in Asian countries, which belongs to the amphetamine-type stimulant class of substances. To detect the chronic drug misuse, human hairs have often been used as analytical specimens due to their long detection windows and easy accessibility. However, there is no investigation regarding the cut-off value of MAMP detection used in black-hair Chinese populations. Based on the analytical data obtained from 563 MAMP users, the cut-off value was found to be 0.97 ng/mg for the simultaneous detection of MAMP and amphetamine (AMP) ≥0.004 ng/mg (LOD). Through the established HPLC-MS/MS analytical method, the limits of detection and quantification of MAMP were 0.004 and 0.01 ng/mg, respectively. The cut-off value was optimized by AMP detection rate and receiver operating characteristic analysis, and the results were consistent with the previously reported MAMP/AMP ratio.


Assuntos
Estimulantes do Sistema Nervoso Central/análise , Cabelo/química , Metanfetamina/análise , Detecção do Abuso de Substâncias/métodos , Grupo com Ancestrais do Continente Asiático , China , Cromatografia Líquida de Alta Pressão , Toxicologia Forense , Humanos , Limite de Detecção , Espectrometria de Massas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
14.
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
15.
Forensic Sci Int ; 307: 110108, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31877542

RESUMO

Quetiapine is an atypical antipsychotic drug, frequently found in post-mortem samples. The quantitative determination of active metabolites may help in the interpretation of the potential toxic effects of the parent drug and its role in death. A fully validated LC-MS/MS method was developed for the identification and quantification of quetiapine and two main metabolites (N-desalkylquetiapine and 7-hydroxyquetiapine) in blood, biological fluids and tissues. Then, the distribution of analytes in different matrices was evaluated. LODs of 0.9, 0.3 and 0.3ng/mL were calculated for quetiapine, N-desalkylquetiapine and 7-hydroxyquetiapine respectively; while a LOQ at the concentration of 10.0ng/mL was defined for the three analytes. 13 post-mortem positive real cases have been included in the experiment. The results revealed that quetiapine and N-desalkylquetiapine might undergo a significant post-mortem redistribution, while 7-hydroxyquetiapine is less affected by this factor. N-desalkylquetiapine could be found in blood in relatively high concentrations in comparison to those of quetiapine; therefore, it should be always advisable to measure both the analytes. The analysis of tissues could provide additional data on potential intoxication with quetiapine.


Assuntos
Antipsicóticos/farmacocinética , Mudanças Depois da Morte , Fumarato de Quetiapina/farmacocinética , Tecido Adiposo/química , Adulto , Idoso , Bile/química , Química Encefálica , Cromatografia Líquida , Dibenzotiazepinas/farmacocinética , Feminino , Toxicologia Forense , Humanos , Rim/química , Limite de Detecção , Fígado/química , Pulmão/química , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/química , Baço/química , Espectrometria de Massas em Tandem , Distribuição Tecidual , Adulto Jovem
16.
Fa Yi Xue Za Zhi ; 35(5): 581-585, 2019 Oct.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31833293

RESUMO

Abstract: Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry (GC-QTOF-MS). Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Delitos Sexuais , Espectrometria de Massas em Tandem/métodos , Tiletamina/análise , Zolazepam/análise , Humanos , Tiletamina/sangue , Zolazepam/sangue
17.
Forensic Sci Int ; 305: 109999, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671355

RESUMO

In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data are limited and provides challenges to toxicologists. The objectives of this study were (1) to develop and validate analytical methods for the determination of synthetic opioids in vitreous humor and brain, and (2) to investigate the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. Vitreous humor (0.5mL) and brain tissue (5g) homogenized in water (diluted 1:3, w/w) were extracted by mixed mode cation exchange-reversed phase solid phase extraction. Extracts were analyzed by liquid chromatography tandem mass spectrometry (LC-MSMS). The chromatographic separation was performed by reversed-phase with 0.1% formic acid in water and in acetonitrile as mobile phases in gradient mode, with a total run time of 21min. Data were acquired with ESI+ in dynamic multiple reaction mode (dMRM), monitoring 2 transitions per compound. The methods were succesfully validated following SWGTOX guidelines, with limits of quantification of 0.1ng/mL in vitreous humor and 0.1ng/g in brain. Fifty-eight authentic case samples from the New York City Office of the Chief Medical Examiner (NYC-OCME) were analyzed to assess the distribution and detectability of synthetic opioids in these postmortem samples. Of the fifteen synthetic opioids included in the method, six synthetic opioids and metabolites (4-ANPP, acetylfentanyl, fentanyl, furanylfentanyl, norfentanyl, U-47700) were detected in the authentic cases. Concentrations for most analytes were within the 0.1 to 100ng/mL or ng/g calibration range across all three matrices, with only concentrations from acetylfentanyl and U-47700 exceeding 100ng/mL or ng/g. The highest concentrations were observed in brain (except norfentanyl), followed by blood and vitreous humor. Most analytes were detected in all three matrices in a given case. This was followed by detection of an analyte in combinations of brain and another matrix or brain only. Through the case analyses, vitreous humor and brain demonstrated to be viable alternatives to blood when performing postmortem analyses of synthetic opioids. Brain exhibited a higher detectability for most analytes when compared to blood and vitreous humor.


Assuntos
Analgésicos Opioides/análise , Química Encefálica , Medicamentos Sintéticos/análise , Corpo Vítreo/química , Analgésicos Opioides/farmacocinética , Cromatografia Líquida , Toxicologia Forense , Humanos , Psicotrópicos/análise , Psicotrópicos/farmacocinética , Extração em Fase Sólida , Medicamentos Sintéticos/farmacocinética , Espectrometria de Massas em Tandem
18.
Forensic Sci Int ; 305: 109970, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629200

RESUMO

Our aim was to investigate the reason for relatively low detection rates for opioids and fentanyl in particular in post-mortem cases in the State of Hamburg. We re-analysed 822 blood samples from two different time periods, 2011/12 and 2016. These samples had been previously analysed in accordance with post-mortem routine by a case selected strategy. All samples were re-analysed with an LC-MS/MS method specific for prescription opioids. The main point in the evaluation was to determine whether the previous analysis strategy had led to underreporting of drug-related deaths (DRD), especially with regard to fentanyl. Another aim was to evaluate changes in prescribing prevalence of opiates and opioids. We compared pharmacy claims data in Hamburg with Germany. The analyses showed that the number of DRD remained unaffected by the new analytical strategy. Detection rates in DRD, however, increased for fentanyl 3.4-fold from 1.2% to 4.1%, buprenorphine from 5.9% to 7.6%, oxycodone from 0% to 1.8%, tilidine from 1.8% to 2.4%. The most frequently detected opioids in DRD cases were methadone (39.4%) and heroin (20%). Prescription rates between 2011-2017 decreased in Hamburg for nearly all opioids, morphine by - 43.5%, buprenorphine - 43%, codeine - 57%, fentanyl - 25%, tilidine -17%, tramadol - 31%, and hydromorphone -6%. Oxycodone, tapentadol, and piritramide prescription rates increased. For Germany, a decrease in the prescription rates for fentanyl was also found during this period (-12.9 %), although not as pronounced as in Hamburg. Prescription rates for methadone were three to greater than five times higher in Hamburg as compared to the German average due to the higher number of substituted persons per inhabitant. Conclusion: Despite the global problem of opioid abuse, there are significant regional differences in the nature and extent of opioid abuse. It is necessary to collect data at the national level to develop appropriate prevention strategies.


Assuntos
Analgésicos Opioides/análise , Fentanila/análise , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/envenenamento , Cromatografia Líquida , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Fentanila/efeitos adversos , Fentanila/envenenamento , Toxicologia Forense , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Espectrometria de Massas em Tandem , Adulto Jovem
19.
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
20.
Forensic Sci Int ; 304: 109941, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31574421

RESUMO

In last years, international and national Institutions have been completely focused on the new psychoactive substances (NPS) phenomenon. Many contrast policies have been planned in order to control their spread. Even scientific entities, such as our Forensic Toxicology Division, have spent time and resources for NPS identification in biological (from clinical and forensic caseworks) and non-biological (seized material) samples. Last reports show a low prevalence of NPS across the Europe and Italy, while the classical drugs are still the main cause of drug-related deaths. In particular, a worrisome datum is represented by the increasing number of deaths due to heroin. Seen these statistics, is the NPS phenomenon overestimated? Is the interest in classical drugs decreased? Were we diverted by NPS?


Assuntos
Tráfico de Drogas/tendências , Psicotrópicos/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Drogas Desenhadas/efeitos adversos , Toxicologia Forense , Humanos , /efeitos adversos
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