Journal of analytical toxicology最新文献

{"title":"Bladder wash: a proof of concept as an alternative specimen for postmortem toxicology.","authors":"Luke N Rodda, Kylie E Candela, Amy P Hart, Ellen G Moffatt, Megan C Farley, Sue Pearring, Karen S Scott","doi":"10.1093/jat/bkaf001","DOIUrl":"10.1093/jat/bkaf001","url":null,"abstract":"<p><p>In postmortem forensic investigation cases where the bladder is voided or dehydrated prior to autopsy, it is possible to wash the bladder with saline to collect the \"bladder wash\" and any residual urine for toxicological analysis. While not conventional, this study aims to determine the use of bladder washes as alternative specimens in postmortem forensic toxicology. Comprehensive drug and alcohol analysis was performed on blood, urine, vitreous humor, and bladder wash samples. Control studies consisted of matched bladder wash and urine samples for comparison. Authentic applicability studies were performed on bladder wash samples in cases where only blood or no urine samples were available. Bladder wash testing via the routine urine methodology was shown to have the appropriate sensitivity and specificity to serve as an alternative specimen. Specificity of the applicability studies was further improved when comparisons were corrected by evaluating individual analytes jointly with their related parent drug or metabolites. Individual and corrected sensitivity and specificity rates of above 99% were typically observed in both comparisons against urine and blood paired samples. Following drug analysis of 31 cases in which only a bladder wash was available, 57 detections from 23 different analytes were detected that otherwise would not have been obtained. This study demonstrates that standardized collection of the easily accessible bladder wash for postmortem toxicological analysis serves forensic toxicologists and pathologists with invaluable information where urine or other biological specimens are not available.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"180-190"},"PeriodicalIF":2.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970663","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}

{"title":"Toxicological evaluation, postmortem case descriptions, and pharmacological activity of N,N-dimethylpentylone and related analogs.","authors":"Melissa F Fogarty, Sara E Walton, Michael T Truver, Grant C Glatfelter, Alex J Krotulski, Donna M Papsun, Michael Lamb, Chris W Chronister, Bruce A Goldberger, Donna Walther, Kristie Barba, Michael H Baumann, Barry K Logan","doi":"10.1093/jat/bkaf002","DOIUrl":"10.1093/jat/bkaf002","url":null,"abstract":"<p><p>Identification of N,N-dimethylpentylone (DMP) in counterfeit \"Ecstasy\" and \"Molly\" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or relevant blood or tissue concentrations of DMP, and even less is known about other structurally related beta-keto methylenedioxyamphetamine analogs on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography-tandem quadrupole mass spectrometry was developed and validated for the quantitation of DMP and five related synthetic cathinones [eutylone, pentylone, N-ethyl pentylone (NEP), N-propyl butylone, and N-cyclohexyl butylone], with chromatographic resolution from isomeric variants and quantitation performed by standard addition. A forensic series of 125 cases is presented for DMP and related analogs, along with pharmacological activity assessments using monoamine transporter and mouse behavioral assays. The blood concentration range for DMP in postmortem forensic cases was 3.3-4600 ng/mL (mean: 320 ± 570 ng/mL, median: 150 ng/mL), whereas pentylone, the primary N-desmethyl metabolite of DMP, was identified in 98% of cases with a concentration range 1.3-710 ng/mL (mean ± SD: 105 ± 120 ng/mL, median: 71 ng/mL). N-Propyl butylone, a newly identified synthetic cathinone, was quantitated in seven cases (mean ± SD: 82 ± 75 ng/mL, median: 50 ng/mL, range: 1.7-200 ng/mL). DMP displayed potent uptake inhibition at the dopamine transporter [half maximal inhibitory concentration (IC50) of 49 nM], with 100-fold weaker potency at the serotonin transporter (IC50 = 4990 nM). DMP was a locomotor stimulant in mice [medium effective dose (ED50) of 3.5 mg/kg] exhibiting potency relatively similar to eutylone, NEP, and pentylone. Our results show that DMP is a psychomotor stimulant associated with adverse clinical outcomes leading to death. Forensic laboratories must continue to update testing methods to capture emerging drugs, with specific emphasis on resolution and identification of isomeric species. Following the scheduling of DMP in early 2024, there could be an anticipated market shift toward a new unregulated synthetic stimulant to replace DMP.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"143-151"},"PeriodicalIF":2.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opioid hair concentrations using retrospective prescription data from a United States workplace testing population.","authors":"G Neil Stowe, Ryan B Paulsen, Michael I Schaffer","doi":"10.1093/jat/bkae101","DOIUrl":"10.1093/jat/bkae101","url":null,"abstract":"<p><p>Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, Psychemedics frequently encounters questions from clients/Medical Review Officers regarding opioid hair concentrations in relation to the amount of opioids taken as part of a prescription. In this article, we have analyzed a large number of real-world examples of opioid hair concentrations following self-reported consumption of an opioid prescription regimen. This dataset provides a reference point of opioid hair concentrations after an extensive aqueous wash that likely corresponds to consumption of an opioid prescription regimen. Practitioners in the field could use this reference to make decisions on the opioid concentration of a hair sample in relation to a client-provided prescription.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"201-207"},"PeriodicalIF":2.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921689","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}

{"title":"Correction to: Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers.","authors":"","doi":"10.1093/jat/bkaf008","DOIUrl":"10.1093/jat/bkaf008","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"e1"},"PeriodicalIF":2.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake.","authors":"Jennifer Liut, Burkhard Madea, Dirk Meißner, Arne Lützen, Sirous Javidi, Cornelius Hess, Michael Krämer","doi":"10.1093/jat/bkae095","DOIUrl":"10.1093/jat/bkae095","url":null,"abstract":"<p><p>The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate [GHB-Pal]) in whole blood as a potential biomarker to extend the detection window of GHB use, e.g. in drug-facilitated sexual assaults. A liquid chromatography-mass spectrometry (LC-MS-MS) method for the quantification of GHB-Pal in whole blood was validated. Whole blood samples were collected from subjects involed in police roadside controls (n = 113) and from narcolepsy patients (n = 10) after the controlled administration of Xyrem® (sodium oxybate). Both sample collectives were previously tested for GHB using two different methods: ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) and gas chromatography-mass spectrometry (GC-MS). In samples from routine police casework, GHB-Pal was detected in 67 out of 113 analysed GHB-positive samples with a mean concentration of 0.8 ng/mL ± 0.5 ng/mL (standard deviation). Among samples that were tested positive for both compounds, no linear correlation was observed between GHB and GHB-Pal concentrations (r = 0.508). In contrast, GHB-Pal was not detected in any of the blood samples analysed from the patients. The absence of GHB and GHB-Pal in the patient cohort may be attributed to the time interval between dose intake and blood collection (approximately 3 and 6 h), during which GHB was eliminated from the body. Furthermore, GHB-Pal was only detectable at a GHB concentration of at least 16 µg/mL, which indicates that endogenous concentrations or low GHB doses may not be sufficient for GHB-Pal formation. Due to missing correlation between both compounds and the lack of GHB-Pal detection several hours after GHB administration, it can be assumed that GHB-Pal in blood is not a suitable biomarker to widen the detection window of GHB.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"73-84"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806782","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}

{"title":"Drug detection in oral fluid and urine after single therapeutic doses of dexamphetamine, lisdexamphetamine, and methylphenidate in healthy volunteers.","authors":"Arne Helland, Sébastien Muller, Olav Spigset, Hege-Merete Krabseth, Miriam Hansen, Ragnhild Bergene Skråstad","doi":"10.1093/jat/bkae097","DOIUrl":"10.1093/jat/bkae097","url":null,"abstract":"<p><p>Dexamphetamine, lisdexamphetamine, and methylphenidate are central stimulant drugs widely used to treat attention-deficit/hyperactivity disorder (ADHD), but poor adherence may lead to treatment failure, and the drugs are also subject to misuse and diversion. Drug analysis in oral fluid may thus be useful for monitoring adherence and misuse. We measured drug concentrations in oral fluid and urine after controlled dosing to investigate detection windows and evaluate the chosen cutoffs. Healthy volunteers ingested single oral doses of 10 mg dexamphetamine (n = 11), 30 mg lisdexamphetamine (n = 11), or 20 mg methylphenidate (n = 10), after which they collected parallel oral fluid and urine samples every 8 h for 4-6 days. Amphetamine (analytical cutoff, oral fluid: 1.5 ng/mL; urine: 50 ng/mL), methylphenidate (oral fluid: 0.06 ng/mL), and ritalinic acid (urine: 500 ng/mL) were analyzed using fully validated chromatographic methods. The median time from ingestion to the last detection in oral fluid was 67 ± 4.9 h (lisdexamphetamine) and 69 ± 8.8 h (dexamphetamine) for amphetamine and 36 ± 2.5 h for methylphenidate. This was comparable to urine (77 ± 5.1 h for lisdexamphetamine, 78 ± 4.5 h for dexamphetamine, and 41 ± 2.4 h for ritalinic acid). The interindividual variability in detection times was large, probably in part due to pH-dependent disposition. Using a logistic regression approach, we found similar detection rates as a function of time since intake in urine and oral fluid with the chosen cutoffs, with a high degree of probability for detection at least 24 h after intake of a low therapeutic dose. This demonstrates the usefulness of oral fluid as a test matrix to assess adherence to ADHD medications, provided that the analytical method is sensitive, requiring a cutoff as low as 0.1 ng/mL for methylphenidate. Detection windows similar to those in urine may be achieved for amphetamine and methylphenidate in oral fluid.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"65-72"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854248","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}

{"title":"Postmortem distribution of MDPHP in a fatal intoxication case.","authors":"Emma Beatrice Croce, Alexandra Dimitrova, Maria Grazia Di Milia, Stefano Pierotti, Davide Arillotta, Marta Barbaresi, Martina Focardi, Fabio Vaiano","doi":"10.1093/jat/bkae092","DOIUrl":"10.1093/jat/bkae092","url":null,"abstract":"<p><p>The synthetic cathinone (SC) 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) is structurally correlated to the 3,4-methylenedioxypyrovalerone (MDPV). In recent years, the number of intoxication cases has increased even if little is known about the pharmacokinetics properties. The Postmortem (PM) distribution of MDPHP remains largely unexplored. In these reports, MDPHP levels were quantified in blood, gastric content, and urine. This study aimed to describe the MDPHP PM distribution in several specimens, i.e. central and peripheral blood (CB and PB), right and left vitreous humor (rVH and lVH), gastric content (GCo), urine (U), and hair. The samples were collected from a cocaine-addicted 30-year-old man with a PM interval estimated in 3-4 h. Autopsy examination revealed unspecific findings, i.e. cerebral and pulmonary edema. No injection marks were observed. Toxicological analyses were performed using a multi-analytical approach: headspace gas chromatography for blood alcohol content (BAC), gas chromatography-mass spectrometry (GC-MS) for the main drugs of abuse, liquid chromatography-tandem mass spectrometry (LC-MS-MS) for benzodiazepines, and new psychoactive substances (NPS). BAC was negative (0.02 g/L). MDPHP concentrations were as follows: 1,639.99 ng/mL, CB; 1,601.90 ng/mL, PB; 12,954.13 ng/mL, U; 3,028.54 ng/mL, GCo; 1,846.45 ng/mL, rVH; 2,568.01 ng/mL, lVH; 152.38 (0.0-1.5 cm) and 451.33 (1.5-3.0 cm) ng/mg, hair. Moreover, hair segments were also positive for 3,4-dimethylmethcathinone (DMMC < limit of quantification: 0.01 ng/mg), α-PHP (0.59 ng/mg, 0.0-1.5 cm; 3.07 ng/mg, 1.5-3.0 cm), cocaine (6.58 ng/mg, 0.0-1.5 cm; 22.82 ng/mg, 1.5-3.0 cm), and benzoylecgonine (1.13 ng/mg, 0.0-1.5 cm; 4.30 ng/mg, 1.5-3.0 cm). MDPHP concentrations were significantly higher than those reported in the literature for fatal cases. For these reasons, the cause of death was probably the consumption of a lethal amount of MDPHP. Because CB and PB were similar, PM redistribution was not relevant.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"137-141"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double designers: detection of bromazolam and metonitazene in postmortem casework.","authors":"Danielle Van Cleve, Mackenzie Liebl, Ani Kazaryan","doi":"10.1093/jat/bkae082","DOIUrl":"10.1093/jat/bkae082","url":null,"abstract":"<p><p>The identification of novel psychoactive substances (NPSs) in casework at the Los Angeles County Department of Medical Examiner (LACDME) is constantly evolving. The case detailed herein marks the first detection of metonitazene (MTZ) in forensic casework at the LACDME, which occurred in August 2023. Furthermore, bromazolam was found in the decedent's system and both substances were identified in drug evidence collected at the death scene. No other drugs were detected and the manner and cause of death were determined as accidental due to effects of bromazolam and MTZ. The concentrations detected were 1.6 ng/mL and 4.4 ng/mL of MTZ in the jugular blood and femoral blood, respectively, and 93 ng/mL of bromazolam in the femoral blood. Constraints in screening techniques conducted by toxicology laboratories create challenges in which numerous NPSs available on the illicit drug market can go undetected. Even if labs detect an NPS in their screening methodology, confirmation methods might not cover every NPS, given the impracticality of labs keeping pace with validations as new NPSs emerge in casework. The significance of testing medical evidence collected at death scenes by drug chemistry analysis becomes crucial when initial toxicology results are negative. In cases where there is evidence of potential drug paraphernalia, this is especially true as it can be pivotal in determining the cause and manner of death.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"134-136"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465976","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}

{"title":"Postmortem diphenhydramine blood concentrations in children.","authors":"H Rachelle Wallage, Marie Elliot","doi":"10.1093/jat/bkae084","DOIUrl":"10.1093/jat/bkae084","url":null,"abstract":"<p><p>Diphenhydramine has been available for decades in non-prescription formulations for the treatment of allergic reactions, insomnia, and symptomology associated with colds. In addition, dimenhydrinate, a precursor to diphenhydramine, is available in preparations for the treatment of nausea and vomiting. Diphenhydramine and other first-generation antihistamines are being replaced by second- and third-generation antihistamines, which are associated with fewer side effects, notably the lack of drowsiness; however, there are still a variety of therapeutic uses that have persisted in both adults and children. In this study, postmortem blood concentrations of diphenhydramine were determined, by liquid chromatography-tandem mass spectrometry, in seven children with concentrations ranging from 0.051 to 2.6 mg/l. The cause of death in two cases was attributed, at least in part, to diphenhydramine toxicity, while diphenhydramine detection in five cases was considered incidental to the cause of death.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"129-133"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500837","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}

{"title":"Optimization of a disposable pipette tips extraction for the analysis of psychoactive substances in sweat specimens using design of experiments.","authors":"Nayna Cândida Gomes, Vítor Luiz Caleffo Piva Bigão, Eduardo Geraldo de Campos, Oscar Cabrices, Bruno Ruiz Brandão da Costa, Bruno Spinosa De Martinis","doi":"10.1093/jat/bkae090","DOIUrl":"10.1093/jat/bkae090","url":null,"abstract":"<p><p>Novel psychoactive substances continue to emerge in the marketplace and are often found as substances in traditional illicit drug materials and users are often unaware of the presence of other drugs. The proper identification and confirmation of the exposure to a drug is made possible when a biological specimen is collected and tested. Sweat is an alternative biological matrix of great interest for clinical and forensic analysis. One of the reasons is attributed to its expanded drug detection window, enabling a greater monitoring capacity, and provision of information on prospective drug use. However, the concentrations of drugs in sweat samples are often low, which requires highly sensitive and selective methods. Disposable pipette tips extraction (DPX) is a new miniaturized solid-phase extraction technique capable of efficiently extracting analytes from biological specimens, providing high recoveries, and requiring minimized solvent use. This study describes the development and optimization of two methods for the extraction of basic and neutral psychoactive substances from sweat samples using gas chromatography-mass spectrometry and Design of Experiments (DoE). The following extraction parameters were optimized by DoE techniques: sample volume, elution solvent volume, washing solvent volume, sample aspiration time, elution solvent aspiration time, and number of cycles performed, including the elution step. It was possible to design a simple extraction protocol that provided optimized recoveries for both basic and neutral compounds. The sum of analyte areas increased at a rate of 54.7% for compounds of basic character and 39.2% for compounds of neutral character. Therefore, our results were satisfactory, demonstrating that DPX can be successfully used for extracting the target drugs from sweat samples.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"104-114"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675883","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}