Journal of analytical toxicology最新文献

{"title":"Development and application of an LC-MS/MS method for 8 antiepileptic drugs and 2 metabolites using microsampling techniques (DBS and VAMS).","authors":"María Cobo-Golpe, Lucía Paniagua-González, Elena Lendoiro, Miriam Blanco-Ces, Ángela López-Rabuñal, Javier Abella, Dolores Castro, Cristina Melcón, Patricia Fuentes, Iria Carballeira, Carlos García, Carmen Gómez, Manuel López-Rivadulla Lamas, Angelines Cruz, Ana de-Castro-Ríos","doi":"10.1093/jat/bkaf073","DOIUrl":"https://doi.org/10.1093/jat/bkaf073","url":null,"abstract":"<p><p>Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is used for optimization and individualization of patients' treatment. Capillary microsampling techniques are a promising alternative to conventional venous sampling for TDM. Both dried blood spots (DBS) and volumetric adsorptive microsampling (VAMS) devices are less invasive and patient-friendly sampling techniques which have been gaining interest in the last years. This study describes the development and validation of an LC-MS/MS method for the determination of 8 AEDs (Carbamazepine, Lacosamide, Levetiracetam, Lamotrigine, Phenobarbital, Valproic acid) and 2 metabolites (10,11-Dihydro-10-hydroxy-carbamazepine (DHCB) and carbamazepine-10,11-epoxide) in DBS and VAMS samples. The method was fully validated for linearity, selectivity, accuracy, precision, carryover, matrix effect, recovery and stability (15 days at room temperature and 72 h in autosampler). Moreover, the volume effect, volcano effect, and the hematocrit (Hct) effect were also assessed for DBS samples. All parameters showed satisfactory results, with a limit of quantification ranging from 0,5 to 10 µg/mL, depending on the analyte. Some instability issues were detected in DBS samples for oxcarbazepine. However, the inclusion of oxcarbazepine's metabolite DHCB overcomes this problem as it was stable under both conditions tested. Moreover, this is the first DBS or VAMS method reporting the inclusion of DHCB, which seems essential for the TDM of oxcarbazepine. The method was applied to 80 paired samples from patients under treatment with these drugs in order to study the suitability of the method for the detection of these compounds, and compare concentrations in paired VAMS, DBS, whole blood and plasma samples. Ratios between paired samples show a promising correlation between microsampling techniques and plasma concentrations.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642618","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":"Balancing the (uncertainty) budget-postmortem toxicology laboratory conformance to ANSI/ASB Standard 056: Standard for Evaluation of Measurement Uncertainty in Forensic Toxicology.","authors":"Joseph H Kahl, Diane M Moore","doi":"10.1093/jat/bkaf068","DOIUrl":"https://doi.org/10.1093/jat/bkaf068","url":null,"abstract":"<p><p>In postmortem forensic toxicology, the accuracy and reliability of toxicological results are critical to the medicolegal death investigation process. ANSI/ASB Standard 056: Standard for Evaluation of Measurement Uncertainty in Forensic Toxicology establishes the minimum requirements for evaluating measurement uncertainty (MU) in quantitative methods utilized in forensic toxicology. Accurate evaluation of MU increases confidence in results, supports scientific rigor, enables inter-laboratory comparability, and ensures legal defensibility. Using the National Institute of Standards and Technology (NIST) 8-step procedure described in ANSI/ASB Standard 056, postmortem forensic toxicology laboratories can develop customized, flexible MU budget templates that accommodate a variety of analytical workflows and sample preparation techniques commonly used in the field. This manuscript highlights the use of a template that is adaptable to both routine quantitative workflows and those employing method of standard addition, providing example MU calculations for each. By aligning laboratory practices with the NIST 8-step procedure, as well as integrating accreditation requirements and published ANSI/ASB Standards into their quality management system, laboratories enhance the accuracy and reliability of their toxicological results. Adhering to ANSI/ASB Standard 056 ensures that the inherent variability in postmortem toxicological analyses is appropriately assessed and managed in a manner consistent with best practices.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637076","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":"Prevalence and Concentration of Fentanyl in Hair Collected for Court-Ordered Mandatory Drug Testing.","authors":"Megan Grabenauer, Nichole D Bynum, Lauren E Johann, Katherine Bollinger, Lisa S Davis, Eugene D Hayes, Ron R Flegel, Ruth E Winecker","doi":"10.1093/jat/bkaf067","DOIUrl":"https://doi.org/10.1093/jat/bkaf067","url":null,"abstract":"<p><p>Hair testing is often employed by court-ordered mandatory drug testing (COMDT) programs, however as of December 2024, many of these programs still do not include fentanyl in their testing panels. Further, testing panels including fentanyl for purposes of workplace testing are rare and concentrations of fentanyl in hair of people who have used drugs are needed to validate future testing cutoffs. In this study we analyzed 1025 hair specimens, originally collected for COMDT purposes, for 26 substances, including 13 fentanyl-related compounds. Methamphetamine was the most detected compound (n = 266, 26%), followed by hydrocodone (n = 157, 15%). Fentanyl was the most detected fentanyl-related compound, followed by 4-ANPP. Fentanyl was detected in 151 (15%) hair specimens. 12 specimens contained a fentanyl-related compound with no detectable fentanyl. Of the 163 specimens in which fentanyl or a fentanyl-related compound was detected 31 (19%) had no other analytes detected. Using a cutoff of 1 pg/mg the detection rate for fentanyl was 14.7%. Conversely, most commercial testing laboratories utilize cutoffs between 20-100 pg/mg. For the 98 specimens with fentanyl concentrations in the quantifiable range (5-2000 pg/mg), the maximum, mean, and median concentrations were 1,946, 223, and 55 pg/mg, respectively. An additional 7 specimens had concentrations greater than the ULOL of 2,000 pg/mg with an estimated maximum fentanyl concentration of 9,246 pg/mg. 44 specimens contained detectable norfentanyl. The norfentanyl: fentanyl ratios ranged from 0.02 to 0.46 with a mean of 0.09. COMDT programs that do not include fentanyl or employ common commercial cutoffs in their testing protocols for fentanyl are potentially missing drug positive specimens.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637077","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":"The detection of cannabinoids in breath after ingestion of cannabis-infused edibles.","authors":"Jennifer L Berry, Ashley Brooks-Russell, Tara M Lovestead, Kavita M Jeerage","doi":"10.1093/jat/bkaf063","DOIUrl":"https://doi.org/10.1093/jat/bkaf063","url":null,"abstract":"<p><p>The increase of Δ9-tetrahydrocannabinol (THC) in breath after cannabis inhalation has been well-documented in the forensic field, but the trends after ingestion of cannabis-infused edibles have not yet been investigated. In this study, participants ingested a cannabis-infused edible and provided breath samples before and at three timepoints after ingestion. Participants were assigned to one of two breath sampling devices. THC was found in most pre-use breath samples and THC concentration had variable trends after ingestion. Nineteen participants exhibited a maximum in their THC concentration at 47 min, 92 min, or 180 min after ingestion, while six participants had their highest THC concentration before the observed ingestion and four participants had no significant change in THC concentration over the four samples. Five additional cannabinoids were detected in breath. While cannabidiol (CBD) trends followed THC trends for some participants, diverging trends in other participants suggest different biological processing of CBD derived from edibles. This proof-of-concept study shows that THC concentration in breath can increase after the ingestion of cannabis-infused edibles, but the uncertainty of breath measurements and a longer time window need to be further explored.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600503","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":"Fatalities following DMT use: Two case reports and a review of the literature.","authors":"Jade Pullen, Robert Moore, Rebecca Wood, Edmund Rab, Lewis Couchman, Caroline S Copeland","doi":"10.1093/jat/bkaf064","DOIUrl":"https://doi.org/10.1093/jat/bkaf064","url":null,"abstract":"<p><strong>Background: </strong>N, N-dimethyltryptamine (DMT) is a hallucinogen found in the South American Psychotria viridis plant and is the major psychoactive ingredient in the brew ayahuasca. In this report we performed a review of the surrounding literature and detail two deaths which recently occurred in the UK following DMT use.</p><p><strong>Methods: </strong>A literature search of both academic (PubMed, GoogleScholar) and media (using Google search engine) publications was performed to identify previously reported fatalities following DMT use. The National Programme on Substance Use Mortality (NPSUM) was also searched for deaths which have occurred in the UK following DMT use.</p><p><strong>Results: </strong>Literature search-There have been three previous reports of fatalities following DMT use, all deemed accidental in nature, with DMT consumption taking place as part of an ayahuasca ceremony in two of these cases.NPSUM cases-Two cases were identified (Case Report 1 [CR1] & Case Report 2 [CR2]), neither of which occurred in the context of an ayahuasca ceremony. DMT was detected and quantified in femoral blood in both cases (CR1 0.23 mg/l; CR2 0.24 mg/l). There was evidence of polydrug use in both cases (CR1 n = 6; CR2 n = 9), which in each case included additional compounds which can increase serotonergic drive (CR1 cocaine, amphetamine; CR2 venlafaxine, mirtazapine).</p><p><strong>Discussion: </strong>There have been two recent deaths following DMT use in the UK, both in the context of polydrug use which may have caused death due to excessive serotonergic innervation leading to serotonin syndrome. Polydrug use is increasingly common in the UK, and users of unregulated drugs should caution their use in combination with other unregulated drugs and also any prescribed medications.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600502","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":"Evaluation of the iScreen™ Urine Test FUO Drug Screen Cup for detection of 17 drugs of abuse in urine.","authors":"James A Goebl, Forch Zhao, Jasmine Zhong, Christopher Green, Sean Han","doi":"10.1093/jat/bkaf062","DOIUrl":"https://doi.org/10.1093/jat/bkaf062","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600485","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":"Exploring transdermal SARMs exposure: Analysis of the elimination profiles and metabolism for doping control purposes.","authors":"Linus Korsmeier, Sophia Krombholz, Hana Alhalabi, Andreas Thomas, Mario Thevis","doi":"10.1093/jat/bkaf066","DOIUrl":"https://doi.org/10.1093/jat/bkaf066","url":null,"abstract":"<p><p>Transdermal drug delivery has been of particular interest to pharmaceutical research for decades, but is also becoming increasingly relevant in the field of sports drug testing. As shown in the past, the (unintentional) oral ingestion of trace amounts of prohibited selective androgen receptor modulators (SARMs), e.g. due to product contamination, can lead to an adverse analytical finding (AAF) in doping controls. Another site of exposure is presented by the skin, as it provides a large surface for drug penetration. However, the extent of diffusion through various layers of the skin and into the blood vessels depends, among other things, on the physicochemical and biological properties of a substance. The objective of this project was to simulate a transdermal contamination scenario and investigate the skin penetration and subsequent metabolism of microdoses of three commonly used SARMs: LGD-4033, RAD140, and S-23. For this purpose, an administration study was conducted, in which either 10 or 50 µg of the substances were applied to the lower forearm of 5 volunteers each. The collected urine samples were analyzed via LC-MS/MS following enzymatic hydrolysis and solid-phase extraction. This methodical approach is distinguished by its high sensitivity, enabling the detection of at least 5 pg/mL for LGD-4033 and S-23. After 10 µg administration, LGD-4033 and S-23 as well as associated metabolites were detected, while RAD140 was only detected in urine samples of one subject (n = 5). Following the application of 50 µg, RAD140 was detected in all subjects (n = 5) for up to 9 days, and additional metabolites of LGD-4033 and S-23 were identified. The long-term metabolite of LGD-4033 (M5b) was detected up to 12 days after the dermal administration of 10 µg, and up to 25 days after application of 50 µg, while S-23 was traceable for up to 16 respectively 24 days. It was demonstrated for all three SARMs that they penetrate the skin and may-even in trace amounts-produce AAFs when administered transdermally. Information on urinary concentrations and metabolism following transdermal administration of SARMs may assist in the interpretation of AAFs, particularly when dermal contamination or intentional doping via the skin is discussed.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600486","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":"Application of Professional Best Practices in Postmortem Forensic Toxicology.","authors":"Michael T Truver, Chris W Chronister, Gregory G Davis, Teresa R Gray, Rebecca L Hartman, Joseph H Kahl, Erin L Karschner, Sarah Kerrigan, Robert Kronstrand, Alex J Krotulski, Dayong Lee, Barry K Logan, Diane M Moore, Luke N Rodda, Svante Vikingsson, Ruth E Winecker, Bruce A Goldberger","doi":"10.1093/jat/bkaf061","DOIUrl":"https://doi.org/10.1093/jat/bkaf061","url":null,"abstract":"<p><p>Postmortem forensic toxicology plays a critical role in medicolegal death investigations through the identification and quantitation of drugs and other substances in postmortem fluids and tissues. Due to the complexity of this sub-discipline, consistent application of best practices is critical for ensuring accurate and reliable results, particularly in the context of challenges such as emerging novel psychoactive substances, complex poly-drug interactions, postmortem drug redistribution, and analytical limitations inherent with postmortem specimens. Although there has been significant progress in the development of consensus-based forensic toxicology standards, their scope is intentionally broad to accommodate human performance, postmortem, regulated and non-regulated employment drug testing, court-ordered toxicology, and other applications. Consequently, some aspects specific to postmortem toxicology and medicolegal death investigation are not addressed within the standards. This manuscript seeks to fill these gaps by demonstrating how current standards can be applied in a postmortem toxicology setting and presenting best practices in situations where no established standards exist. These best practices will aid laboratories in prioritizing changes to workflows, allocating resources more efficiently, improving analytical accuracy and reproducibility, ensuring interpretative consistency, and strengthening forensic defensibility in administrative and legal proceedings. Key topics addressed include specimen collection and case submission protocols, method validation approaches tailored for postmortem analysis, optimized analytical workflows based on testing scope and case classification, and quality assurance requirements. Considerations for data review, reporting, and result interpretation are discussed in the context of accurate determination of cause and manner of death. Emphasis is placed on integrating toxicological findings with investigative and autopsy information obtained through ongoing communication with stakeholders. By integrating the application of existing consensus standards with the best community practices for postmortem toxicology, this manuscript aims to support the generation of robust and reliable toxicological data, with the goal of improving forensic investigations, public health surveillance, and drug policy development.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600484","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":"A New Automated Method for the Analysis of Cotinine and trans-3'-Hydroxycotinine in Serum by LC/MS/MS.","authors":"Danielle L Hopkins, Madeline L Weaver, Connie Sosnoff, Rayaj Ahamed, Lanqing Wang, Tiffany H Seyler","doi":"10.1093/jat/bkaf059","DOIUrl":"10.1093/jat/bkaf059","url":null,"abstract":"<p><p>Tobacco cigarette smoking is the leading cause of preventable diseases and death in the US. Exposure to secondhand smoke (SHS) can also cause heart disease, lung cancer, and respiratory illness. Cotinine (COT) and trans-3'-hydroxycotinine (HCT) are the primary metabolites of nicotine, the main addictive alkaloid in tobacco products. For many years, we have measured serum levels of COT and HCT in National Health and Nutritional Examination Survey (NHANES) participants to monitor exposure of the U.S. population to active smoking and SHS. As exposure to SHS is decreasing, a more sensitive analytical method is needed to detect the lower levels of these biomarkers for SHS assessment. We developed and validated a new automated method for the detection of COT and HCT in human serum. We implemented a new liquid handling automation system to aliquot and prepare samples using supported liquid extraction. Samples were analyzed by liquid chromatography-tandem mass spectrometry. The new automated sample preparation method increases sample throughput by reducing sample cleanup time to 2 hours for preparing a 96-well plate. The method has excellent sensitivity, specificity, precision (<10%), and accuracy (±15%). We were able to lower the estimated limit of detection (LOD) for COT by 33% and HCT by 73% from our previous LOD. The new LODs for COT and HCT are 0.010 ng/mL and 0.004 ng/mL, respectively. These lower LODs would enable better detection of SHS in future NHANES surveys.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560182","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":"Testing for trazodone, an antidepressant, in hair collected from horses.","authors":"Pascal Kintz, Morgane Baudry, Laurie Gheddar","doi":"10.1093/jat/bkaf025","DOIUrl":"10.1093/jat/bkaf025","url":null,"abstract":"<p><p>Trazodone, a medicine registered for human, is a serotonin agonist-antagonist. At low dose, the drug is sedative due to its antagonist properties. At high dose, it is an agonist with anxiolytic and antidepressant actions. Trazodone can be administered to the horse to reduce anxiety. However, according to the antidoping rules for horses, the presence of trazodone in blood or urine is considered as a violation, which will produce a suspension of both the athlete and the horse as the drug is listed banned on the International Federation of Horseracing Authorities prohibited substances list. As a hair test can provide more evidence or supplementary information to an adverse analytical finding or to document drug exposure, our forensic laboratory received two specimens with a request for trazodone identification. After mane collection, trazodone was analysed by a new LC-MS/MS method involving pH 9.5 borate buffer overnight incubation of 20 mg of specimen in presence of clozapine-d4 used as internal standard, followed by solvents extraction. Linearity was verified from 1 to 100 pg/mg (R2 = 0.9967). Limit of detection of the method was 0.1 pg/mg. Trazodone was measured at 0.4 pg/mg in the mane of a horse suspended after an antidoping violation. In a case of hidden administration, trazodone was identified at 9 and 24 pg/mg in two consecutive mane hair segments. Although no controlled study allows interpretation, particularly about the frequency of exposure and the dose that entered in the body, this is the first evidence that trazodone can be incorporated in the mane of horses.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":"401-406"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633848","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}