Journal of analytical toxicology最新文献

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HIV combination drug therapies: development and validation of an LC-MS-MS method for simultaneous quantitation of abacavir, dolutegravir, and lamivudine in rat matrices in support of toxicology studies. HIV联合药物治疗:同时定量大鼠基质中阿巴卡韦、多替格拉韦和拉米夫定的LC-MS/MS方法的开发和验证,以支持毒理学研究。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-16 DOI: 10.1093/jat/bkaf016
Melanie A Rehder Silinski, Jennifer A Gilliam, Julia Apoian, Brenda L Fletcher, Reshan A Fernando, Suramya Waidyanatha
{"title":"HIV combination drug therapies: development and validation of an LC-MS-MS method for simultaneous quantitation of abacavir, dolutegravir, and lamivudine in rat matrices in support of toxicology studies.","authors":"Melanie A Rehder Silinski, Jennifer A Gilliam, Julia Apoian, Brenda L Fletcher, Reshan A Fernando, Suramya Waidyanatha","doi":"10.1093/jat/bkaf016","DOIUrl":"10.1093/jat/bkaf016","url":null,"abstract":"<p><p>Abacavir (ABC), Dolutegravir (DTG), and Lamivudine (3TC) are part of a fixed-dose combination medication for the treatment of HIV. The three drugs offer different but complementary mechanisms of action by inhibiting reverse transcriptase and integrase, and ultimately inhibiting HIV replication. Due to the lack of information regarding long-term safety following in utero exposure, we are evaluating potential toxicity to offspring following in utero exposure to this combination therapy in Hsd:Sprague Dawley®SD® (HSD) rats, including cardiovascular toxicity and neurotoxicity. Generating internal exposure data are integral to putting toxicological findings into context. The objective of this work was to develop and validate a method to simultaneously quantitate ABC, DTG, and 3TC in rat matrices following exposure to this combination. The method used protein precipitation of plasma, fetal, placental, brain, or heart homogenate, followed by ultra-performance liquid chromatography-tandem mass spectrometry. In adult Sprague Dawley rat plasma, the method was linear (r ≥ 0.99) over the range 10/15/5 to 10,000/15,000/5000 ng/mL for ABC/DTG/3TC and recovery was ≥92% for all three analytes at all concentration levels. The limits of detection were 2.22, 3.69, and 0.978 ng/mL for ABC, DTG, and 3TC, respectively. Intra- and inter-day precision was ≤8.7% relative standard deviation (RSD), and relative error (RE) ≤±12.0% for standards prepared at 20/30/10, 400/600/200, and 5000/7500/2500 ng/mL. Matrix standards as high as 40/60/20 µg/mL could be diluted into the calibration range (RE≤±3.5% and RSD ≤2.4%). The method was evaluated for HSD rat maternal plasma and fetal, placental, brain, and heart homogenates (mean RE ≤±15.0% and RSD ≤8.6%). Analyte stability was demonstrated in extracted plasma for 2 days at different temperatures, and in various matrices stored at -80°C for at least 32 days (80-113% of Day 0 concentrations). These data demonstrate that this simple and efficient method is suitable for quantitation of ABC, DTG, and 3TC in rat matrices generated from toxicology studies. The method can easily be adapted to other biological matrices and species (e.g. human).</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"332-339"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of a dried blood spot screening test using gas chromatography coupled to high-resolution mass spectrometry: application in authentic postmortem samples. 使用气相色谱法和高分辨率质谱法的干血斑点筛选试验的发展:在真实尸检样本中的应用。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-16 DOI: 10.1093/jat/bkaf011
Denis Dubois-Chabert, Estelle Flament, Guillaume Hoizey, Camille Chatenay, Laurent Fanton, Charline Bottinelli
{"title":"Development of a dried blood spot screening test using gas chromatography coupled to high-resolution mass spectrometry: application in authentic postmortem samples.","authors":"Denis Dubois-Chabert, Estelle Flament, Guillaume Hoizey, Camille Chatenay, Laurent Fanton, Charline Bottinelli","doi":"10.1093/jat/bkaf011","DOIUrl":"10.1093/jat/bkaf011","url":null,"abstract":"<p><p>This study aims to develop a toxicological screening analysis using gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS) on postmortem dried blood spots (DBSs) and apply it to authentic cases. Twenty-five microliters of blood was deposited and dried on a paper card. Compounds of interest were desorbed, extracted, and acetylated, then injected into the GC-HRMS. The limits of detection (LOD) and of identification (LOI) were determined for 22 of the compounds that were most frequently detected in postmortem blood samples in the laboratory in 2022. Stability on DBS was studied at three temperatures (-20°C, +4°C, and +20°C) over 15 days. The method was then applied to 102 postmortem blood samples. Results were compared to the two conventional screening methods implemented in the laboratory: liquid chromatography coupled with diode-array detection and mass spectrometry (LC-DAD-MS) and GC-MS. Selectivity was demonstrated by the analysis of 10 negative postmortem blood samples. All LODs were between <10.0 and 20.0 ng/mL. LOIs were within the therapeutic concentration range for each compound or at a value not leading to acute intoxication (narcotics). Overall, compounds remained stable over the 15 days at all test temperatures, except for midazolam and tramadol and its metabolites. A comparison of screenings of 102 postmortem samples resulted in 239 identifications, corresponding to 74 compounds, across 70 positive cases. In 32 cases, no compound was identified. Compounds of 57% and 60%, respectively, were detected by LC-DAD-MS and GC-MS screenings, while DBS-GC-HRMS identified 81%. Application of the method to a hundred authentic cases demonstrated its ability to meet the constraints of low sample volume, sensitivity, and ease of preservation for urgent cases or cases with limited blood availability.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"340-350"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toxicological and demographic profiles of phencyclidine-impaired driving cases in Houston: updates from the 2019 to 2023 data. 休斯顿苯西利定(PCP)酒后驾驶病例的毒理学和人口学特征:2019-2023年数据的更新
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-16 DOI: 10.1093/jat/bkaf021
Dayong Lee, Salvador R Corral, Cassandra Duvall, Peter Stout
{"title":"Toxicological and demographic profiles of phencyclidine-impaired driving cases in Houston: updates from the 2019 to 2023 data.","authors":"Dayong Lee, Salvador R Corral, Cassandra Duvall, Peter Stout","doi":"10.1093/jat/bkaf021","DOIUrl":"10.1093/jat/bkaf021","url":null,"abstract":"<p><p>Phencyclidine (PCP) is a dissociative anesthetic harmful to road traffic safety as the drug may impair driving performance by inducing adverse effects such as sedation, ataxia, agitation, disorientation, and confusion. Houston Forensic Science Center previously reported toxicological and demographic characteristics of PCP-impaired driving cases in Houston from 2013 to 2018 and presently reports the 2019-23 cases. The blood samples collected from suspect drivers were analyzed for alcohol and drugs and those positive for PCP at the reporting limit of 5 ng/mL were included in the study (n = 1375). The drivers had the median (mean, range) PCP concentration of 45 (49, 5-170) ng/mL and were mostly males (77%) and black (89%) with the mean age of 40 years. More than half of the drivers (59%) were polydrug users with cannabinoids being the most frequently detected (39%), followed by cocaine/metabolites (15%) and ethanol (10%). Compared to our previous findings and other studies, the PCP concentration distributions and concurrent drug profiles of the drivers were remarkably consistent despite multiple changes in the drug market over the years; their demographics also remained comparable except for the mean age, which continued to increase. Continual surveillance of PCP-impaired driving cases is important to identify risk groups and aid in reducing this hazardous driving behavior, so prevalent and persistent in the city of Houston.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"358-363"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toxicological detection of the new psychoactive substances MDPHP and MDPHpP in human urine samples by elucidation of their urinary metabolites using gas chromatography-mass spectrometry. 气相色谱-质谱联用分析新型精神活性物质MDPHP和MDPHpP在人尿中的毒理学检测。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-16 DOI: 10.1093/jat/bkaf026
Isabel Brueckner, Jessica Welter-Luedeke, Claudia Gutjahr-Ruhland, Matthias Graw, Liane D Paul
{"title":"Toxicological detection of the new psychoactive substances MDPHP and MDPHpP in human urine samples by elucidation of their urinary metabolites using gas chromatography-mass spectrometry.","authors":"Isabel Brueckner, Jessica Welter-Luedeke, Claudia Gutjahr-Ruhland, Matthias Graw, Liane D Paul","doi":"10.1093/jat/bkaf026","DOIUrl":"10.1093/jat/bkaf026","url":null,"abstract":"<p><p>The continuous emergence of new psychoactive substances on the illicit drug market provides challenges for forensic and clinical analytics. Reliable detection of previous ingestion of these drugs in human urine samples requires elucidation of target metabolites and, in the case of gas chromatography-mass spectrometry (GC-MS), the knowledge of their derivatized mass spectra. The study presented here focused on the two pyrrolidinophenones 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 3,4-methylenedioxy-α-pyrrolidinoheptanophenone (MDPHpP), which could be identified in 25 and 3 authentic cases, respectively. Using a standard analytical procedure by means of full-scan GC-MS after acid hydrolysis and acetylation, phase I metabolites of both substances were identified in authentic urine samples by elucidation of their mass spectral fragmentation patterns. The postulated phase I metabolic steps of MDPHP and MDPHpP comprised demethylenation followed by methylation of the methylenedioxy moiety, oxidation of the pyrrolidine ring, N,N-bisdealkylation of the pyrrolidine ring to its primary amine, and hydroxylation of the aliphatic side chain. Various combinations were detected. Acetylated mass spectra of the metabolites were provided for both substances. The analogy in mass fragmentation of the proposed metabolites for the homologous parent compounds indicated a high plausibility. Based on the frequency of occurrence and abundances of the metabolites in the urine samples, target analytes for both substances and base peak fragment ions for specific mass search could be recommended for the mentioned procedure: m/z 140, 154, and 86 for MDPHP and m/z 154, 168, and 100 for MDPHpP. The study could support the detection of these new substances in forensic and clinical cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"299-314"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Psychoactive cocktail consumption on Reunion Island: a case report. 留尼汪岛上的精神鸡尾酒消费:一例报告。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-16 DOI: 10.1093/jat/bkaf009
Joris Guyon, Adrien Maillot, Sophie Bastard, Flore Weisse, Amélie Daveluy, David Mété
{"title":"Psychoactive cocktail consumption on Reunion Island: a case report.","authors":"Joris Guyon, Adrien Maillot, Sophie Bastard, Flore Weisse, Amélie Daveluy, David Mété","doi":"10.1093/jat/bkaf009","DOIUrl":"10.1093/jat/bkaf009","url":null,"abstract":"<p><p>Reunion Island is a French department located in the southwestern Indian Ocean, with distinct trends in drug use, drug diversion, and intoxication compared with metropolitan France (e.g. the misuse of drugs-clonazepam and trihexyphenidyl-combined with cannabis or cocaine, which is not observed in metropolitan France). The authors report a case of atypical intoxication in a 16-year-old female who consumed cannabis in conjunction with an unusual powdered mixture containing psychotropic substances. The intoxication led to confusion, hallucinations, sinus tachycardia, and hospitalization. A comprehensive high-resolution mass spectrometry and liquid-chromatography mass spectrometry analysis of her plasma, her urine and a powder found in her possession revealed the presence of the same five medicines: citalopram/escitalopram, paroxetine, sertraline, venlafaxine, and trihexyphenidyl. This case underscores the intricate interactions between psychoactive substances that are never prescribed together in clinical settings, along with the issue of diverted prescription drugs like trihexyphenidyl. It also emphasizes the potential circulation and use of crushed mixtures of medication for recreational purpose. Fortunately, powder analysis provided crucial insight to understand the intoxication.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"369-373"},"PeriodicalIF":2.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Δ9-tetrahydrocannabinol in venous and capillary blood following ad libitum cannabis smoking by occasional and daily users. 偶尔吸食和日常吸食大麻后静脉和毛细血管血Δ9-tetrahydrocannabinol的比较。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-14 DOI: 10.1093/jat/bkaf043
G Dooley, S Godbole, J Wrobel, T Henthorn, A Brooks-Russell, S Limbacher, M Kosnett
{"title":"Comparison of Δ9-tetrahydrocannabinol in venous and capillary blood following ad libitum cannabis smoking by occasional and daily users.","authors":"G Dooley, S Godbole, J Wrobel, T Henthorn, A Brooks-Russell, S Limbacher, M Kosnett","doi":"10.1093/jat/bkaf043","DOIUrl":"10.1093/jat/bkaf043","url":null,"abstract":"<p><p>Δ9-Tetrahydrocannabinol (Δ9-THC) is the most prominent and main psychoactive cannabinoid found in cannabis. In forensic matters involving cannabis, such as drugged driving or workplace accident investigations, blood Δ9-THC determination is typically required. Venipuncture by a phlebotomist at a medical facility is often the standard blood collection protocol, but this procedure is time consuming and requires specialized training. Capillary blood collection at the site of a transportation or workplace mishap may provide a collection method that is logistically easier and may better reflect blood cannabinoid concentrations at the time of an incident. This study represents the first temporal comparison of the concentration of Δ9-THC and its primary metabolites in venous and capillary blood obtained from users following ad libitum inhalation of contemporary high-concentration cannabis products. Participants provided their own cannabis from a licensed Colorado dispensary and were instructed to smoke or vape ad libitum the amount most used for the desired effect during a 15-minute period. Capillary blood samples collected at the lateral shoulder using the TAP® II microneedle device and standard venipuncture samples at the forearm were collected contemporaneously at baseline and then 10, 30, 60, 90, and 140 minutes after the last inhalation and were analyzed for Δ9-THC, 11-hydroxy-Δ9-THC, and 11-carboxy-Δ9-THC by liquid chromatography tandem mass spectrometry. Within-subject Δ9-THC concentrations trended lower, often up to 30 to 40%, in contemporaneous capillary blood samples than in venous blood samples until 140 min after cannabis smoking. Concentrations of the Δ9-THC metabolites 11-hydroxy-Δ9-THC and 11-carboxy-Δ9-THC were equivalent at all but the first timepoint after smoking. Due to logistical advantages, capillary blood collection by microneedle devices may be a viable option for qualitative detection of Δ9-THC and its metabolites soon after an incident or a quantitative determination if the samples are collected at least 2 hours after cannabis inhalation.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protonitazene metabolite variability in post-mortem casework. 死后病例中原硝唑代谢物的变异性。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-12 DOI: 10.1093/jat/bkaf042
Rebecca Wood, Robert Moore
{"title":"Protonitazene metabolite variability in post-mortem casework.","authors":"Rebecca Wood, Robert Moore","doi":"10.1093/jat/bkaf042","DOIUrl":"https://doi.org/10.1093/jat/bkaf042","url":null,"abstract":"<p><p>Protonitazene is a highly potent synthetic opioid that has recently emerged in the illicit drug supply. Data on its metabolism and the detection of its metabolites in post-mortem specimens are limited. This study retrospectively analysed 14 post-mortem cases to investigate metabolite profiles in blood and urine using high-resolution mass spectrometry. Detected metabolites included 5-aminoprotonitazene, N-desethylprotonitazene, and 4-hydroxynitazene. Additionally, a novel metabolite, hydroxyprotonitazene, previously only observed in liver microsome models, was identified. Significant variability in the metabolites detected across cases was observed, likely influenced by differences in metabolism, post-mortem changes, sampling methods, and metabolite stability. This study underscores the challenges of detecting protonitazene exposure and highlights the necessity of targeting multiple metabolites, as no single marker reliably indicated protonitazene use. Further research is needed to confirm metabolite identities, evaluate their stability, and understand their role in protonitazene toxicity.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drug transfer during intimate moments can produce an adverse analytical finding during a doping control. Case report with ligandrol. 亲密时刻的药物转移可能在兴奋剂检查中产生不利的分析结果。ligandrol 1例报告。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-08 DOI: 10.1093/jat/bkaf041
Pascal Kintz, Laurie Gheddar
{"title":"Drug transfer during intimate moments can produce an adverse analytical finding during a doping control. Case report with ligandrol.","authors":"Pascal Kintz, Laurie Gheddar","doi":"10.1093/jat/bkaf041","DOIUrl":"https://doi.org/10.1093/jat/bkaf041","url":null,"abstract":"<p><p>Selective androgen receptor modulators (SARMs) are a new class of substances that have similar properties to anabolic steroid agents, but with marked reduced androgenic properties. As SARMs have the potential to be misused for performance enhancement in sport due to their anabolic properties as well as ability to stimulate androgen receptors in the muscle and the bone, they have been prohibited at-all-times by the World Anti-Doping Agency (WADA) since 2008 under section S1.2 of the List. Ligandrol is one of the more popular SARMs. A WADA accredited laboratory identified in the urine of a female athlete bishydroxy-ligandrol, the major ligandrol metabolite at approx. 90 pg/mL (specimen A) and 200 pg/mL (specimen B). The athlete challenged this anti-doping rule violation and requested a hair test to document possible incidental exposure. About 7 weeks after urine collection, a hair specimen (brown in color and > 20 cm in length) was collected and segmented in 6 x 1 cm segments. Ligandrol was tested by liquid chromatography-tandem mass spectrometry after alkaline incubation and extraction. With a limit of quantitation at 1 pg/mg, no ligandrol was identified. It appears that the athlete was unaware her husband was taking the substance, which was confirmed by his hair test (ligandrol at 7 and 8 pg/mg in 2 x 2.5 cm segments). The Court of Arbitration for Sports accepted the athlete's explanation that she had been exposed to ligandrol through the exchange of bodily fluids with her husband and lifted her provisional ban. This case demonstrates that drug transfer between two subjects is possible during intimate moments.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Medetomidine Quantitation and Enantiomer Differentiation in Biological Specimens Collected After Fatal and Non-Fatal Opioid Overdoses. 致死性和非致死性阿片类药物过量后采集的生物标本中美托咪定的定量和对映体分化。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-08 DOI: 10.1093/jat/bkaf040
Sara E Walton, Brianna N Stang, Sherri Kacinko, Donna M Papsun, Barry K Logan, Alex J Krotulski
{"title":"Medetomidine Quantitation and Enantiomer Differentiation in Biological Specimens Collected After Fatal and Non-Fatal Opioid Overdoses.","authors":"Sara E Walton, Brianna N Stang, Sherri Kacinko, Donna M Papsun, Barry K Logan, Alex J Krotulski","doi":"10.1093/jat/bkaf040","DOIUrl":"https://doi.org/10.1093/jat/bkaf040","url":null,"abstract":"<p><p>Medetomidine is an alpha-2 agonist and non-opioid sedative. Its presence in illicit fentanyl and heroin drug supplies poses significant risks to user health caused by cardiac effects and sedation. Medetomidine exists in two enantiomeric forms: dexmedetomidine and levomedetomidine. Dexmedetomidine is used in humans in medical settings, while dexmedetomidine alone and a racemic mixture of dexmedetomidine and levomedetomidine are used in animals in veterinary settings. Little information is known about circulating blood concentrations of medetomidine or its enantiomers in humans in situations involving synthetic opioids (e.g., fentanyl) and other sedatives (e.g., xylazine, benzodiazepines). A new toxicological workflow using liquid chromatography tandem quadrupole mass spectrometry (LC-QQQ-MS) was developed and validated for the quantitation of medetomidine and the qualitative enantiomeric separation of dexmedetomidine and levomedetomidine. The assays were applied to a case series of 100 authentic specimens from emergency department admissions and forensic postmortem investigations containing medetomidine, fentanyl, xylazine, and metabolites, among other substances. Medetomidine blood concentrations in non-fatal overdoses ranged 0.1-16 ng/mL (median: 1.5 ng/mL) and in fatal overdoses ranged 0.1-32 ng/mL (median: 0.31 ng/mL). Xylazine was co-detected in 76% of cases with higher median concentrations: 8.3 ng/mL (non-fatal) and 15 ng/mL (fatal). Fentanyl was co-detected in 93% of cases with median concentrations of 5.2 ng/mL (non-fatal) and 21 ng/mL (fatal). Dexmedetomidine and levomedetomidine were identified in 90% of cases; the remaining cases were confirmed or suspected medical-setting administration of dexmedetomidine. These findings demonstrate that medetomidine is arising from veterinary or clandestine sources, and we hypothesize the latter. Recreational medetomidine use causes adverse effects such as profound bradycardia and heightened sedation, especially when combined with fentanyl and xylazine. Forensic laboratories must remain aware of adulterants, like medetomidine, appearing in traditional opioid products (e.g., fentanyl, heroin), updating testing methods to capture these emerging adulterants in real-time.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethanol production in the gut: An autopsy case. 肠道乙醇生产:一个尸检案例。
IF 2.3 3区 医学
Journal of analytical toxicology Pub Date : 2025-05-05 DOI: 10.1093/jat/bkaf039
Maiko Kusano, Chikara Kohda, Masaya Fujishiro, Taka-Aki Matsuyama
{"title":"Ethanol production in the gut: An autopsy case.","authors":"Maiko Kusano, Chikara Kohda, Masaya Fujishiro, Taka-Aki Matsuyama","doi":"10.1093/jat/bkaf039","DOIUrl":"https://doi.org/10.1093/jat/bkaf039","url":null,"abstract":"<p><p>Postmortem alcohol production by microorganisms has been known to increase blood alcohol concentration, potentially leading to erroneous interpretation. Here, we present a peculiar case where postmortem toxicology detected a high ethanol concentration only in the stomach content. An 87-year-old bedridden female was taken to senior day care facility, where the nurse attempted to take her vitals but noticed she was not breathing. The facility called for an ambulance but she was pronounced dead soon after arriving at the hospital. She was found to be severely dehydrated and her blood tests indicated poor health. Autopsy was performed two days after death, and postmortem alcohol analysis detected a high ethanol concentration only in the stomach content. Our aim was to investigate the causative agent of ethanol production; microbiological analysis identified the yeast species Candida glabrata as the responsible microorganism.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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