Journal of analytical toxicology最新文献

{"title":"Quantification of kratom alkaloids mitragynine, 7-hydroxy mitragynine, mitragynine pseudoindoxyl, and dihydro-7-hydroxy mitragynine (MGM-15) in forensic casework and medicolegal death investigations.","authors":"Lauren K Eccarius, Sara E Walton, Donna M Papsun, Barry K Logan, Alex J Krotulski","doi":"10.1093/jat/bkag090","DOIUrl":"https://doi.org/10.1093/jat/bkag090","url":null,"abstract":"<p><p>Mitragynine (MG) is the primary psychoactive component of the kratom plant (Mitragyna speciosa). 7-Hydroxy mitragynine (7OH-MG) is found naturally in the plant but in small amounts (<2%). MG is metabolized to 7OH-MG and further to mitragynine pseudoindoxyl (MP), with the latter documented via in vitro enzymatic activity. Lack of scheduling has caused unregulated markets to proliferate with gas stations, smoke shops, and online retailers selling semi-synthetic formulations of these alkaloids under the umbrella term \"kratom,\" though distinct from botanical kratom. Products containing 7OH-MG, MP, and synthetically derived dihydro-7-hydroxy mitragynine (DH-7OH-MG, aka MGM-15) exhibit greater potencies and activities at the µ-opioid receptor compared to MG and are now highly implicated in intoxications and deaths. These alkaloids present complex analytical and interpretive challenges due to their isomeric forms, incompatibility with certain extraction and instrumental techniques promoting analyte interconversion, instability in blood, and lack of published concentration ranges. A quantitative high-resolution mass spectrometry method for MG, 7OH-MG, MP, and DH-7OH-MG, which prevents interconversion and separates isomers, is presented herein along with stability data and concentrations from more than 200 authentic cases. MG, MP, and DH-7OH-MG were relatively stable in blood, whereas 7OH-MG decreased quickly and by 89% over 112 days with concurrent increase in MP. In a case subset (n = 139), mean ± SD concentrations in blood were 146 ± 477 ng/mL for 7OH-MG (median: 58 ng/mL, range: 0-5,000 ng/mL) and 194 ± 239 ng/mL for MP (median: 120 ng/mL, range: 4.8-1,900 ng/mL). In a second subset (n = 17), the mean ± SD DH-7OH-MG concentration was 324 ± 669 ng/mL (median: 170 ng/mL, range: 50-2,900 ng/mL). Testing for kratom alkaloids is currently extremely limited and/or subject to potential inaccuracy due to interconversion, leaving adverse events and fatalities under-investigated. Continued vigilance is needed as the kratom alkaloid product landscape rapidly evolves.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194161","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":"Comment on Chang et al.: defining the added interpretive value of brain fentanyl testing at low blood concentrations.","authors":"Ercan Yilmaz, Zeynep Yamancan Yilmaz","doi":"10.1093/jat/bkag088","DOIUrl":"https://doi.org/10.1093/jat/bkag088","url":null,"abstract":"<p><p>Chang et al. report substantial variability in fentanyl blood-to-brain relationships and suggest that brain testing may be beneficial in suspected overdose cases with low peripheral blood concentrations. We suggest that this implication would be strengthened by distinguishing analytical confirmation from incremental forensic interpretation. Demonstrating fentanyl in a second matrix does not itself establish that the brain result changes attribution of fentanyl's role in death. A focused analysis of low-blood cases in which brain findings altered interpretation, supported by scene, autopsy, and co-intoxicant data, would better define the practical value of brain testing.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166691","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":"Evaluating Post-Analytical Stability of Blood Ethanol Samples Using Headspace-GC-FID.","authors":"David Cook, Jarrad Wagner","doi":"10.1093/jat/bkag089","DOIUrl":"https://doi.org/10.1093/jat/bkag089","url":null,"abstract":"<p><p>The analysis and determination of blood alcohol concentration (BAC) is a cornerstone test in forensic toxicology that is well researched. The purpose of this study was to determine the post analytical stability of blood ethanol obtained from re-injected vials via Agilent dual column headspace-GC-FID. Over 6 months and 22 individual batch analyses, 303 samples were prepared and analyzed using Headspace-GC-FID for the presence of blood ethanol using 0.02% n-propanol as an internal standard. Each individual batch was re-injected after storage at room temperature for 72 hours to mimic a typical weekend absence. Ethanol signal response, n-propanol signal response and measured blood ethanol concentration were evaluated for stability in terms of percent change. Sample population consisted of negative human blood fortified with known concentrations of ethanol via certified reference material purchased from accredited vendors (n = 187) in the form of calibrators and controls, as well as unknown post-mortem and ante-mortem blood samples submitted to the Nassau County Medical Examiner's Office Department of Forensic Toxicology (n = 116). All samples were tested using similar conditions and internal standard. Significant differences were observed in the signal response for both n-propanol (p<.001) and ethanol (p<.001) between the two test groups however, there was a non-significant difference in measured BAC between the two groups t(302) = 0.3, p = 0.780, d = 0.016. Results suggest very little effect of re-injection after 72-hour storage at room temperature on measured blood ethanol concentration using headspace GC-FID. While there was significant loss of ethanol and internal standard on reinjection, the calculated ethanol concentration was unaffected due to the similar properties of both volatile measurands as well as the consistency of the response ratio of ethanol:n-propanol in reinjected vials. In addition, the observed differences in measured BAC on re-injection were well within the NCME's measurement uncertainty of 11% at k = 3.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136650","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":"Paraphenylenediamine Poisoning: Clinical Spectrum, Analytical Determination, and Challenges in Postmortem Interpretation.","authors":"Muhammad Imran, Imtiaz Majeed, Muhammad Zaman","doi":"10.1093/jat/bkag087","DOIUrl":"https://doi.org/10.1093/jat/bkag087","url":null,"abstract":"<p><p>Paraphenylenediamine (PPD), the principal ingredient of oxidative hair dyes, is a growing cause of acute poisoning in developing nations. This paper provides a comprehensive overview of published case reports, observational studies of PPD poisoning, clinical manifestations, current management strategies, analytical methods for PPD detection, and offers key clinical and post-mortem toxicology considerations. A literature search related to PPD poisoning was conducted from 1991 to 2025 across PubMed, Scopus, Web of Science, and Google Scholar. Publications encompassing 6,843 individual cases were reviewed, and data on demographics, dose, route, clinical features, laboratory parameters, treatment modalities, outcomes, and analytical approaches were analyzed. Angioedema, rhabdomyolysis, and acute renal failure form a characteristic clinical triad that is almost universal in moderate-to-severe cases, with mortality rates ranging up to 55.5% in hospital cases. Cardiac and hepatic injury are also common. PPD has no specific antidote, and treatment is completely supportive. Analytical methods ranging from colorimetric screening to confirmatory tandem mass spectrometry for PPD detection in biological and non-biological matrices are discussed. This review strongly suggests that PPD poisoning represents a significant public health concern in the developing world. Young women with low socioeconomic and rural backgrounds predominantly ingested PPD with suicidal intent. The highest fatality rates were observed in cases where treatment was delayed due to late diagnosis, primarily because no point-of-care test is currently available for the rapid detection of PPD. The combination of lethality, availability, and accessibility makes PPD an ideal agent for suicidal poisoning in populations with high rates of impulsive suicidal behavior. Early diagnosis can improve survival rates in PPD poisoning cases.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109898","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":"Intoxications and fatalities associated with the ingestion of the novel synthetic cathinone, N-isopropyl butylone.","authors":"Munchelou M Gomonit, Sara E Walton, Michael T Truver, Chris W Chronister, Donna M Papsun, Alex J Krotulski, Bruce A Goldberger, Barry K Logan","doi":"10.1093/jat/bkag079","DOIUrl":"10.1093/jat/bkag079","url":null,"abstract":"<p><p>Synthetic cathinones represent an expanding class of novel psychoactive substances (NPS), with their proliferation largely driven by international drug control measures and the rapid cycling of structural analogues designed to circumvent legislative scheduling. Following the international control of N, N-dimethylpentylone (DMP) in 2024, N-isopropyl butylone (NiPB) was increasingly detected in forensic toxicological casework as the prevalence of DMP declined. However, limited data currently exist regarding NiPB's concentration ranges in forensic investigations. This report describes a validated liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS) method for the quantitation of NiPB in biological specimens, which was applied to the analysis of drugged driving (n = 1) and postmortem (n = 15) cases. The driving under the influence of drugs case yielded a NiPB blood concentration of 16 ng/mL, whereas the remaining 15 cases demonstrated blood concentrations ranging from <1 to 1400 ng/mL. For one case, NiPB was quantitated in blood, vitreous fluid, and urine, with concentrations of 18, 17, and 2200 ng/mL, respectively. Polydrug use was observed for all cases and frequently involved fentanyl (75%), cocaine and/or methamphetamine (69%), other synthetic cathinones (25%), ethanol (31%), and additional NPS such as bromazolam (19%) and MDMB-4en-PINACA (13%). Concentrations overlapped between antemortem and postmortem cases and were comparable to those reported for structurally related beta-keto methylenedioxyamphetamines, suggesting that members of this analogue class may share similar patterns of use and toxicological profiles. Although NiPB was identified as a contributing factor in several fatalities, the lack of pharmacological and toxicological data limits further interpretation of measured concentrations and the extent of its contribution to these fatal outcomes. Additional studies incorporating paired central and peripheral blood specimens are warranted to better characterize potential postmortem redistribution and its impact on NiPB blood concentration interpretation. Overall, this case series addresses a critical literature gap on NiPB by providing analytical and interpretive data to support forensic laboratories as NiPB identifications increase within the evolving NPS stimulant market.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955971","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":"Detection and quantification of carbon monoxide in postmortem liver tissues via headspace GC-MS as an alternative to blood.","authors":"Aracelis A Velez, Rebecca A Phipps","doi":"10.1093/jat/bkag076","DOIUrl":"10.1093/jat/bkag076","url":null,"abstract":"<p><p>Carbon monoxide (CO) is a gas that is readily absorbed by the lungs when inhaled. Once in the blood, it forms a complex with hemoglobin (Hb) in red blood cells known as carboxyhemoglobin (COHb), reducing the oxygen-carrying capacity of Hb and therefore disrupting the transport and delivery of oxygen throughout the body. The resulting lack of oxygen can be harmful and even lethal, making it important to be able to detect COHb in postmortem samples of relevant cases for determining a cause of death. Blood and spleen are the preferred specimens for the detection of CO because they are Hb rich, but these specimens may not always be available for collection during autopsy. This study aims to determine if liver tissue can be a reliable source for the detection and/or quantification of CO in postmortem specimens in the absence of blood or spleen. Liver homogenates and blood specimens from 25 postmortem cases with a positive CO result in blood (%COHb ≥10%) and 10 postmortem cases testing negative for CO in blood (%COHb <10%) were analyzed for COHb via headspace gas chromatography/mass spectrometry (HS-GC/MS) and compared. Cases for which the blood produced a positive result for CO did not always result in a positive finding in the liver (%COHb ≥10%), even in cases with high levels of %COHb saturation (>50%). However, all cases that had a liver result ≥10% COHb had a corresponding blood result ≥10% COHb. If blood or spleen is not available for CO testing, liver may be tested as a potential indicator of CO exposure. A positive %COHb finding in the liver is a reliable indicator of a positive %COHb result in blood, but negative results in liver are inconclusive and cannot rule out CO exposure.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891553","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":"Urinary detection and metabolite profiles of trenbolone and metenolone following trace-level dermal exposure.","authors":"Sophia Krombholz, Yiannis A Angelis, Gregor Fußhöller, Mario Thevis","doi":"10.1093/jat/bkag085","DOIUrl":"10.1093/jat/bkag085","url":null,"abstract":"<p><p>Recent studies have demonstrated that dermal exposure to anabolic androgenic steroids (AAS) can result in adverse analytical findings (AAFs) in doping controls with a comparably long detectability of the parent compound and/or their metabolites in urine samples. Transdermal absorption is influenced by multiple factors, including physicochemical properties of the substance and solubility; but is largely driven by the degree of exposure, i.e. amount of substance applied. Therefore, this study aimed to investigate the detectability and urinary excretion profiles of trenbolone (TREN) and metenolone (MET) after dermal exposure to microgram quantities of these frequently abused AAS. Controlled excretion studies were conducted with healthy male volunteers, and each participant received a single dose of 50 µg TREN or MET via dermal application to the forearm. Urine samples were collected and analyzed for the parent compounds and their metabolites by liquid chromatography coupled to high resolution tandem mass spectrometry (LC-HRMS/MS). To enhance sensitivity and product ion formation, derivatization with Girard's reagent T was employed for MET and its metabolites. Following administration of transdermal microdoses, both substances and/or their metabolites were detectable in the urine samples of all participants. For TREN, predominantly the established main metabolite epitrenbolone was identified, with maximum concentrations up to 2.6 ng/ml and a detection window of up to 3 days post-application. Maximum concentrations of MET ranged from 0.1 to 1.2 ng/ml. Notably, particularly the sulfoconjugated metabolite of MET remained detectable for over a week in one volunteer. Metabolite profiles were compared with those of urine samples obtained after oral administration of the steroids to assess potential differences. Considering the increasing number of alleged transdermal contamination cases, the results provide important analytical data to better assess the plausibility of such claims.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989723","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":"Impact of buccal cell content and swab retention on tetrahydrocannabinol and cocaine concentrations in oral fluid.","authors":"Franck Saint-Marcoux, Nathan Campos Lapa, Sylvain Dulaurent, Pauline Griffeuille, Souleiman El Balkhi","doi":"10.1093/jat/bkag084","DOIUrl":"10.1093/jat/bkag084","url":null,"abstract":"<p><p>While oral fluid (OF) is increasingly used in forensic and roadside toxicology, measured drug concentrations remain highly dependent on pre-analytical conditions. This study investigated the impact of buccal-cell content and sample fractionation on concentrations of delta 9-tetrahydrocannabinol (THC), cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME). Oral-fluid specimens were collected using FLOQSwabs®. Following elution, sonication, and vortex mixing, various fractions (homogenate, pellet, and expressed swab) were analyzed via liquid chromatography-tandem mass spectrometry. For THC (n = 102), median buccal epithelial cell counts and THC concentrations were significantly higher in the cell-rich pellet than in the homogenate (P < .001), with median enrichment ratios of 4.40 and 3.93, respectively. The association between cellular and THC enrichment was strong to very strong (r = 0.77-0.88) for concentrations above 5 ng/mL. Notably, four specimens were below the limit of detection in the homogenate but detectable in the pellet. In contrast, cocaine and its metabolites showed comparable concentrations between the homogenate and pellet, though the expressed swab fraction consistently yielded the highest levels. In 52 specimens, median expressed swab-to-homogenate ratios were 1.16 for cocaine, 1.28 for BZE, and 1.14 for EME. These findings demonstrate that pre-analytical effects are analyte-dependent: buccal cells act as a reservoir for THC, whereas cocaine-related analytes are primarily affected by incomplete release from the swab. These results identify analyte-dependent pre-analytical sources of variability that may affect oral-fluid concentration measurements obtained with this collection device.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001917","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":"Therapeutic drug monitoring-guided management of venlafaxine overdose in an adolescent: a case report.","authors":"Michaela Krivošová, Nela Žideková, Zuzana Kubisová, Tomáš Bělohlávek, Veronika Kucianová, Slavomír Nosál', Martin Kertys","doi":"10.1093/jat/bkag080","DOIUrl":"10.1093/jat/bkag080","url":null,"abstract":"<p><p>This report describes an adolescent with severe venlafaxine intoxication in whom serial therapeutic drug monitoring (TDM) was performed, enabling detailed toxicokinetic characterization throughout the clinical course. The initial plasma concentration of the active venlafaxine moiety was 7800 ng/mL, nearly 20 times the upper therapeutic reference limit. On admission, the patient presented with tachycardia, bilateral mydriasis, and generalized tonic-clonic seizures, which are typical clinical manifestations of severe venlafaxine intoxication. Due to progressive impairment of consciousness and increasing oxygen requirements, the patient underwent orotracheal intubation and remained on mechanical ventilation for nearly 120 hours. Serial measurements of venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), provided valuable information on the toxicokinetic progression and supported clinical decision-making regarding the timing of extubation. Despite the extremely elevated venlafaxine concentration, cardiotoxicity was limited to transient QTc prolongation without ventricular arrhythmias and moderate elevations of high-sensitivity troponin I (hs-troponin I) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Marked elevations of creatine kinase and myoglobin concentrations were most likely attributable to rhabdomyolysis following general tonic-clonic seizures. TDM demonstrated a progressive increase in the ODV/venlafaxine metabolite-to-parent ratio from 0.30 to 4.50, reflecting the transition from the acute intoxication phase to the elimination phase. The apparent elimination half-life was prolonged to 14.4 hours for venlafaxine and 17.7 hours for ODV. Genotyping revealed the COMT rs4680 Met/Met genotype, which may theoretically influence catecholamine metabolism; however, its contribution to the clinical presentation remains uncertain.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968757","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":"Strengthening global NPS surveillance: the role of United Nations Office on Drugs and Crime Early Warning Advisory data.","authors":"Marie Belle Kathrina M Hlela, Jared A Brown","doi":"10.1093/jat/bkag078","DOIUrl":"10.1093/jat/bkag078","url":null,"abstract":"","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945112","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}