Journal of analytical toxicology最新文献

{"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217515/pdf/","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":"OA","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}

{"title":"Quantification of ∆9-tetrahydrocannabinol, 11-OH-THC, THC-COOH, hexahydrocannabinol, and cannabidiol in human plasma and blood by liquid chromatography-tandem mass spectrometry.","authors":"Marion Pavlic, Carolin Innerhofer, Florian Pitterl","doi":"10.1093/jat/bkae094","DOIUrl":"10.1093/jat/bkae094","url":null,"abstract":"<p><p>Ongoing legalization of cannabis for recreational use contributes to increasing numbers not only of incidents of driving under the influence, but within all forensic fields. In addition, newly emerging cannabinoids such as hexahydrocannabinol (HHC) and the increasing use of cannabidiol (CBD) products have to be addressed. The aims of this study were first to extend laboratory analysis capacity for the \"established\" cannabinoid ∆9-tetrahydrocannabinol (THC) and its metabolites 11-OH-THC and THC-COOH in human plasma/blood, and second to develop analytical procedures concerning HHC and CBD. An LC-MS-MS method based on the available (low-end) instrumentation was used. Samples (250 µl) were prepared by protein precipitation and solid-phase extraction. Chromatographic separation was achieved on a reversed-phase C18 column within 15 min. Detection was performed on a 3200 QTRAP instrument (Sciex) in positive multiple reaction monitoring (MRM) mode. Matrix-matched six-point calibrations were generated applying deuterated internal standards for all analytes except HHC. The method was fully validated according to GTFCh guidelines. Linear ranges were 0.5-25 µg/l for THC, 11-OH-THC, HHC and CBD, and 2.0-100 µg/l for THC-COOH, respectively. Limits of detection and limits of quantification were 0.5 and 1.0 µg/l (THC, 11-OH-THC, HHC, CBD), and 2.0 and 4.0 µg/l (THC-COOH). Applicability of plasma calibrations to blood samples was demonstrated. Acceptance criteria for intra- and inter-day accuracy, precision, extraction efficiency, and matrix effects were met. No interfering signals were detected for 80 exogenous compounds. The presented method is sensitive, specific, easy to handle, and does not require high-end equipment. Since its implementation and accreditation according to ISO 17025, the method has proven to be fit for purpose not only in driving under the influence of drug cases but also within postmortem samples. Furthermore, the design of the method allows for an uncomplicated extension to further cannabinoids if required.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"85-95"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828825","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":"Postmortem distribution of mitragynine and 7-hydroxymitragynine in 51 cases.","authors":"Kei A Osawa, Robert D Johnson","doi":"10.1093/jat/bkae099","DOIUrl":"10.1093/jat/bkae099","url":null,"abstract":"<p><p>The prevalence of mitragynine (kratom) in forensic toxicology casework has steadily increased over time. Readily available and currently legal, mitragynine is widely used for its stimulant and, depending on concentration, sedative effects. Our laboratory analyzed various fluid and tissue specimens from 51 postmortem cases to investigate the distribution of mitragynine and its active metabolite 7-hydroxymitragynine. Central and peripheral blood concentrations were compared, with an average heart blood to femoral blood ratio being 1.37 for mitragynine and 1.08 for 7-hydroxymitragynine. This ratio >1.0 suggests that mitragynine has some propensity toward postmortem redistribution; however, the difference in concentrations of mitragynine and 7-hydroxymitragynine is not statistically significant. Large average mitragynine to 7-hydroxymitragynine ratios of 30.9 in femoral blood and 32.4 in heart blood were observed compared to average ratios of 14.8 in vitreous humor and 16.9 in urine. In addition, the stability of these two compounds was investigated in both matrix and organic solvent. When stored refrigerated (4°C), mitragynine was stable for up to 30 days and 7-hydroxymitragynine was stable for up to 7 days with an analyte loss of <20%. Following 60 days of refrigerated storage, 7-hydroxymitragynine concentrations dropped over 50% from initial concentrations. Methanolic preparations of mitragynine and 7-hydroxymitragynine were stable following 3 months of storage at -20°C.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"122-128"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949242","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":"LC-MS-MS confirmation of 11-nor-9-carboxy-tetrahydrocannabinol (Δ8, Δ9, Δ10) and hexahydrocannabinol metabolites in authentic urine specimens.","authors":"Amy L Patton, Luette Muir, Joshua Z Seither, Jeffrey P Walterscheid, Erin L Karschner","doi":"10.1093/jat/bkae091","DOIUrl":"10.1093/jat/bkae091","url":null,"abstract":"<p><p>Recently, tetrahydrocannabinol (THC) isomers and other semi-synthetic cannabinoids have been introduced into the consumer market as alternatives to botanical cannabis. To assess the prevalence of these potential new analytical targets, a liquid chromatography-tandem mass spectrometry confirmation method was developed for the quantitation of seven cannabinoid metabolites and the qualitative identification of four others in urine. The validated method was applied to authentic urine specimens that screened positive by immunoassay (50 ng/mL cutoff; n = 1300). The most commonly observed analytes were 11-nor-9-carboxy-Δ8-THC (Δ8- THCCOOH) and Δ9-THCCOOH, with the combination of the two being the most prominent analyte combination found. In addition to these metabolites, Δ10-THCCOOH was observed in 77 specimens. This is the first study to report Δ10-THCCOOH in authentic urine specimens, with this analyte always appearing in combination with Δ9-THCCOOH. Cross-reactivity studies were performed for (6aR,9R)-Δ10-THCCOOH using the Beckman Coulter EMIT® II Plus Cannabinoid immunoassay and demonstrated cross-reactivity equivalent to the Δ9-THCCOOH cutoff, providing added confidence in the reported prevalence and detection patterns. Additionally, 11-nor-9(R)-carboxy-hexahydrocannabinol (9(R)-HHCCOOH) was the most abundant stereoisomer (n = 12) in specimens containing HHC metabolites alone (n = 14). This is in contrast to 9(S)-HHCCOOH, which was the predominant stereoisomer in specimens containing Δ8- and/or Δ9-THCCOOH. Although HHC and Δ10-THC metabolites are emerging toxicology findings, based on these specimens collected between April 2022 and May 2024, an analytical panel containing Δ8- and Δ9-THCCOOH appears to be sufficient for revealing cannabinoid exposure within workplace monitoring and deterrence programs.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"96-103"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716319","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":"Trends in central/peripheral ratio of fentanyl in Harris County, TX, and Orange County, CA, from 2009 to 2020.","authors":"Grayce Behnke, Dani Mata, Vanessa Meneses, Erin C Strickland, Teresa R Gray","doi":"10.1093/jat/bkae093","DOIUrl":"10.1093/jat/bkae093","url":null,"abstract":"<p><p>Since the opioid epidemic was declared in 2017, postmortem fentanyl cases and the need for interpretation of their results have increased. Postmortem redistribution (PMR) is one of the factors to consider when interpreting cases. There have been several previous studies regarding fentanyl PMR; however, these studies either have small sample sizes or were conducted prior to the declaration of the opioid epidemic, which may cause conflicting results and not be reflective of current trends. This study includes fentanyl central/peripheral (C/P) blood ratios from 748 cases from both Harris County, TX, and Orange County, TX, spanning from January 2009 to June 2022. Because the data set was determined to be non-normally distributed, a Kruskal-Wallis test was used for statistical comparisons. There were statistically significant differences between epidemic cases from the Harris County Institute of Forensic Sciences and the Orange County Crime Laboratory, C/P ratios from pre-epidemic to epidemic years, and in cases where medically related administration of fentanyl was documented when compared to cases where there was no documentation of licit fentanyl use. Various factors that could impact PMR were evaluated (age, gender, polydrug use, etc.), and no clear trend or observation was made from the data. Based on the results of this study, there is still no clear indication as to what caused the increase in C/P ratios, but it may be related to an increase in illicit fentanyl use.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"115-121"},"PeriodicalIF":2.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739551","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":"NSC-ADID position statement on performance impairment in safety-sensitive positions related to cannabis and other cannabinoids.","authors":"Michael R Corbett, Sabra R Jones, Ruth E Winecker, Tate Yeatman","doi":"10.1093/jat/bkae089","DOIUrl":"10.1093/jat/bkae089","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"63-64"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675882","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}