Willi Schirmer, Sara E Walton, Wolfgang Weinmann, Stefan Schürch, Barry K Logan, Alex J Krotulski
{"title":"Rapid LC-QTOF-MS screening method for semi-synthetic cannabinoids in whole blood.","authors":"Willi Schirmer, Sara E Walton, Wolfgang Weinmann, Stefan Schürch, Barry K Logan, Alex J Krotulski","doi":"10.1093/jat/bkaf095","DOIUrl":"10.1093/jat/bkaf095","url":null,"abstract":"<p><p>Semi-synthetic cannabinoids are a class of new psychoactive substances (NPSs) with structural similarities to the main psychoactive phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) found in Cannabis sativa L. The first semi-synthetic cannabinoids, which were used as legal substitutes for marijuana, were Δ8-tetrahydrocannabinol (Δ8-THC) and hexahydrocannabinol (HHC). Δ8-THC emerged around 2019 on the recreational drug market in the United States after it became legal due to an ambiguity in the Agricultural Improvement Act 2018 (Farm Bill 2018). It was never legal outside the United States as the isomers of THC are regulated in the United Single Convention on Narcotic Drugs from 1971. HHC, a hydrogenated derivative of THC, followed as a legal substitute on the European recreational drug market. Many countries already placed HHC in their narcotic substance law, which led to the emergence of other structurally related derivatives of THC. An existing rapid screening method for the qualitative analysis of various new psychoactive substances was expanded for semi-synthetic cannabinoids in whole blood using a LC-QTOF-MS system. This method was validated for 24 different phytocannabinoids and semi-synthetic cannabinoids in blood. Recovery rates of the analytes from a liquid-liquid-extraction ranged from 87% to 118%, matrix effects ranged from 24% to 93%, and limits of detection (LOD) ranged from 0.8 to 16 ng/mL.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336870","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}
Gary M Reisfield, Scott A Teitelbaum, Kent T Mathias, Joseph T Jones, Ben Lewis
{"title":"Extended urinary opiate detection following ad libitum ingestion of poppy seed pastry.","authors":"Gary M Reisfield, Scott A Teitelbaum, Kent T Mathias, Joseph T Jones, Ben Lewis","doi":"10.1093/jat/bkaf086","DOIUrl":"10.1093/jat/bkaf086","url":null,"abstract":"<p><p>The interpretation of urine drug test results is complicated by the potential for poppy seed ingestion to yield opiate concentrations above standard cutoffs. US federally regulated workplace drug testing programs have adjusted thresholds over time to mitigate this confounder, but the introduction of low cutoffs in clinical settings has reintroduced interpretive challenges. Fifteen adult participants consumed, ad libitum, a portion of a poppy seed kolachi. Urine samples were collected over 5 days and analyzed for codeine and morphine. Detection windows were evaluated across cutoffs ranging from 4000 ng/mL to the assays' limits of detection (8 ng/mL codeine; 10 ng/mL morphine). Opiate detection duration was inversely related to cutoff. At the 4000 ng/mL cutoff, eight participants were codeine-positive at 8 h, with two participants remaining positive at 24 h. At this cutoff, a single participant was morphine-positive through the first 12 h. At 2000 ng/mL, only codeine remained detectable, in a single participant, at 48 h. At 300 ng/mL, seven participants were opiate-positive at 48 h (only codeine, n = 4; only morphine, n = 2; codeine and morphine, n = 1), and four remained positive at 72 h (only codeine, n = 2; only morphine, n = 2). At 50 ng/mL, five participants were opiate-positive at 96 h (only codeine, n = 2; only morphine, n = 2; codeine and morphine, n = 1). Four participants continued to produce detectable opiate concentrations at 108 h (codeine only, n = 1; morphine only, n = 1; codeine and morphine, n = 2). A single ingestion of a commercial poppy seed kolachi produced urinary opiate concentrations exceeding cutoffs from 4000 ng/mL down to the assays' limits of detection, with positivity persisting up to 108 h. These findings underscore the need for cautious interpretation of positive results-especially in settings using low cutoffs-and support the potential utility of adjunctive markers such as thebaine.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033182","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}
Nichole D Bynum, E Dale Hart, Katherine Bollinger, Eugene D Hayes, Ronald R Flegel, Lisa S Davis, Megan Grabenauer, Ruth E Winecker
{"title":"In vitro formation of hydroxy metabolites of cocaine and amphetamines in hair after hair product exposure.","authors":"Nichole D Bynum, E Dale Hart, Katherine Bollinger, Eugene D Hayes, Ronald R Flegel, Lisa S Davis, Megan Grabenauer, Ruth E Winecker","doi":"10.1093/jat/bkaf094","DOIUrl":"10.1093/jat/bkaf094","url":null,"abstract":"<p><p>In hair drug testing for cocaine, the presence of hydroxycocaine metabolites has been suggested as a means of distinguishing between externally contaminated hair and positive hair due to ingestion of drug. However, hydroxy compounds can also be produced by the action of certain hair products containing peroxides or other reactive chemicals. In this study, hair samples contaminated with cocaine, benzoylecgonine, methamphetamine, and amphetamine were treated with three hair products: a relaxer containing calcium hydroxide, bleaching colorant containing hydrogen and ammonium hydroxide, and a dye containing hydrogen peroxide to determine the effect of the chemical agents on the drug compounds. Authentic positive hair from people who used drugs were treated with the same hair products. Analysis of the contaminated hair showed that the relaxer removed most of the contaminating drugs with trace production of hydroxy compounds. The peroxide-containing hair products resulted in less reduction in parent drug concentrations and higher concentrations of hydroxy compounds. Analysis of hydroxy to parent compound ratios, specifically for para- and meta-hydroxycocaine, showed that no samples produced ratios at 0.05% or higher-a ratio that has been suggested as indicating drug ingestion. With the authentic drug-positive hair, treatment with the products reduced parent and metabolite concentrations while not affecting hydroxy metabolite to parent ratios.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307781","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}
Lena Midtlyng, Gudrun Høiseth, Rafika Rahho, Cecilie Hasselø Thaulow
{"title":"Exploring the \"poppy seed defense\" in oral fluid: detection of opioids following poppy seed consumption.","authors":"Lena Midtlyng, Gudrun Høiseth, Rafika Rahho, Cecilie Hasselø Thaulow","doi":"10.1093/jat/bkaf088","DOIUrl":"10.1093/jat/bkaf088","url":null,"abstract":"<p><p>The \"poppy seed defense\"-a claim that a positive opioid test result is due to ingestion of poppy seeds-is occasionally encountered in forensic toxicology. The matter has been thoroughly investigated in urine but is less researched in oral fluid. We therefore aimed to perform an experimental study to explore whether consumption of commercially available poppy seeds would lead to detection of opioids in oral fluid. Additionally, we aimed to relate our findings to routine cases. Ten volunteers consumed either five crispbreads containing a small amount of poppy seeds, or 30 g of raw poppy seeds with a low opioid content (3.0 mg/kg morphine and 0.9 mg/kg codeine). Oral fluid samples were collected 0.5 and 2 hours after consumption. Additionally, a urine sample was collected 2 hours after consumption. Following ingestion of raw seeds, morphine was detected (estimated neat oral fluid concentrations 1.4-5.6 ng/mL) in all oral fluid samples 0.5 hours after consumption and in one (2.4 ng/mL) of five oral fluid samples after 2 hours. Codeine was detected (0.8-1.1 ng/mL) in three of five oral fluid samples 0.5 hours after consumption, but in none after 2 hours. Following ingestion of crispbreads, morphine or codeine was not detected in oral fluid, but opioids/-glucuronides were detected in three of five urine samples. When comparing our results with routine cases, we found that 14% of routine cases had morphine concentrations in oral fluid samples lower or similar to those seen after ingestion of raw seeds in our experimental study. In conclusion, we found that consumption of raw seeds led to detection of opioids in oral fluid, but the detection window appeared to be short. Comparison with routine cases indicated that the poppy seed defense may be a challenge when interpreting oral fluid results, particularly when low cut-off levels are applied.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131064","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}
Svante Vikingsson, Ruth E Winecker, Katherine Bollinger, Lawrance D Mullen, Tory R Spindle, Ryan Vandrey, Edward J Cone, Lisa S Davis, Ronald R Flegel, Eugene D Hayes
{"title":"Cannabidiol metabolites identified by LC-QTOF after controlled dosing.","authors":"Svante Vikingsson, Ruth E Winecker, Katherine Bollinger, Lawrance D Mullen, Tory R Spindle, Ryan Vandrey, Edward J Cone, Lisa S Davis, Ronald R Flegel, Eugene D Hayes","doi":"10.1093/jat/bkaf098","DOIUrl":"10.1093/jat/bkaf098","url":null,"abstract":"<p><p>Cannabidiol (CBD) is a non-intoxicating cannabinoid found in cannabis and often used for its purported therapeutic benefits. In the form of Epidiolex®, CBD is an FDA-approved treatment for seizure disorders in children. After the 2018 Farm Bill removed hemp (cannabis with <0.3% THC) from the Controlled Substance Act in the United States, non-pharmaceutical CBD became widely available on the retail market. With increased use of CBD, it is important to measure CBD in various biological matrices. In urine, previous studies have measured 7-hydroxy-CBD and 7-carboxy-CBD, analogous to the major metabolites of Δ9-tetrahydrocannabinol (THC). The aim of this study was to identify metabolites of CBD and verify if 7-hydroxy-CBD and 7-carboxy-CBD are the major metabolites. To identify CBD metabolites, 34 urine samples collected after controlled dosing of 100 mg CBD, representing a wide range of time points (1.5-22 hours), and formulations (Epidiolex, syrup, and vaporized administration) were analyzed by liquid-chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) with and without hydrolysis and compared to 11 samples collected after placebo dosing. Thirteen CBD metabolites were identified, including hydroxylation, carboxylic acid formation, alkyl loss, and dihydrodiol formation. The most abundant metabolites included 7-hydroxy-CBD, 6α-hydroxy-CBD, and a novel metabolite indicating hydroxylation on the pentyl sidechain. Most metabolites were >90% conjugated demonstrating that hydrolysis is required for detection in urine. After oral dosing, metabolite concentrations were higher in urine samples collected 4 and 6 h after dosing compared to 1.5 and 11-22 h. CBD concentrations were higher when CBD was administered as Epidiolex compared to synthetically derived CBD in oral syrup or vaping. In conclusion, the results support the use of 7-hydroxy-CBD as a marker of CBD exposure in hydrolyzed urine but also identified several novel metabolites that might further our understanding of CBD pharmacokinetics.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477053","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":"Effect of hemoglobin on the concentration of etizolam in postmortem blood determined by liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.","authors":"Yoshikazu Yamagishi, Kazuaki Takahashi, Hiroyuki Inoue, Sayaka Nagasawa, Hirotaro Iwase, Yasumitsu Ogra","doi":"10.1093/jat/bkaf101","DOIUrl":"10.1093/jat/bkaf101","url":null,"abstract":"<p><p>Etizolam (EZM), a benzodiazepine drug, is a derivative of thienodiazepine. EZM displays an array of biological activities, including as an amnesic, anxiolytic, hypnotic, and muscle relaxant. Given that EZM is associated with instances of lethal intoxication and suicide, it is crucial to establish its exact levels in postmortem (PM) blood. However, EZM concentration at autopsy often diverges from that at the point of death. Here, we demonstrate EZM undergoes hydroxylation and/or oxidation in a mixture of hemoglobin (Hb) and hydrogen peroxide (H2O2) at temperatures between 4 to 45°C. Mass spectrometry combined with liquid chromatography analysis showed the formation of 1-(4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1, 2, 4]triazolo[4,3-a][1, 4]diazepin-2-yl)ethan-1-ol (α-hydroxyetizolam, M1), 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1, 2, 4]triazolo[4,3-a][1, 4]diazepin-6-ol (M2) and 1-(4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1, 2, 4]triazolo[4,3-a][1, 4]diazepin-2-yl)ethan-1-one when EZM was incubated with Hb/H2O2. M1 and M2 were detected in the PM blood of individuals who had died after ingestion of drug, carbon monoxide poisoning, heart attack or choking, following deliberate ingestion of EZM. Our results show that M1 and M2, formed by Hb/H2O2-mediated PM EZM decomposition, are potential biomarkers that can be used to correct the EZM concentration in PM blood.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482104","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}
Ivan Langa, Carolina Rocha-Pereira, Paula Silva, Nuno Milhazes, Diana Dias da Silva, Susana Domingues, Albina Dolores Resende, Joana Barbosa, Juliana Faria, Maria Elizabeth Tiritan, Cláudia Ribeiro
{"title":"Enantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposure.","authors":"Ivan Langa, Carolina Rocha-Pereira, Paula Silva, Nuno Milhazes, Diana Dias da Silva, Susana Domingues, Albina Dolores Resende, Joana Barbosa, Juliana Faria, Maria Elizabeth Tiritan, Cláudia Ribeiro","doi":"10.1093/jat/bkaf103","DOIUrl":"10.1093/jat/bkaf103","url":null,"abstract":"<p><p>Synthetic cathinones are a class of new psychoactive substances (NPS) with 3-chloromethcathinone (3-CMC) accounting for over 46% of NPS-related seizures in 2023. Sold as a racemate, 3-CMC exhibits enantioselective metabolism and pharmacological effects, making enantioselectivity a critical factor in evaluating its toxicokinetics and toxicodynamics. This study aimed to evaluate the enantiomeric biodistribution, metabolic profile, and toxicity of 3-CMC racemate in Wistar rats following acute exposure. For this purpose, a gas chromatography-mass spectrometry (GC-MS) method was validated for quantifying 3-CMC in biological matrices and for characterizing its biodistribution in vivo. Rats were intraperitoneally administered with saline (control) or 3-CMC (10 or 20 mg kg-1, b.w.). Animals were sacrificed 24 h after administration, and plasma, urine, and tissues were collected for biodistribution, biochemical, and histopathological analyses. 3-CMC was exclusively detected in the urine, along with three additional pairs of enantiomeric metabolites. Both 3-CMC and its metabolites exhibit enantiomeric fractions (EF) different from 0.5, indicating enantiomeric enrichment. Administration of 3-CMC significantly decreased plasma levels of creatine kinase-MB, alkaline phosphatase, and aspartate aminotransferase, along with increased levels of glucose and urea. In the urine, decreased levels of albumin were observed. Oxidative stress and energy biomarkers were altered in the brain, lungs, and kidneys. Histopathological analysis revealed morphological alterations in the brain, liver, and lungs at both doses, and in the kidneys at the highest dose. However, no significant alterations were observed in the other tissues. Taken together, our findings suggest enantioselective metabolism and indicate that, although rapidly eliminated by the kidneys, 3-CMC still causes significant toxicity in target organs, such as the brain, liver, lungs, and kidneys. This highlights the high toxicity of the drug or its metabolites, even over short-term exposure.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540788","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}
Roman Papoušek, Vladimíra Gebauerová, Marie Staňková, Petr Handlos, Edita Červenková, Denisa Ptáčková, Lucie Borovcová
{"title":"A highly sensitive headspace gas chromatographic method fully optimized for fast routine determination of carboxyhemoglobin in postmortem blood.","authors":"Roman Papoušek, Vladimíra Gebauerová, Marie Staňková, Petr Handlos, Edita Červenková, Denisa Ptáčková, Lucie Borovcová","doi":"10.1093/jat/bkaf089","DOIUrl":"10.1093/jat/bkaf089","url":null,"abstract":"<p><p>In some cases, the determination of carboxyhemoglobin (COHb) concentration in postmortem blood using standard spectrophotometric methods, may be either impossible or yield misleading results. In forensic laboratories, there is an increasing need to analyze COHb saturation in autopsy blood samples, the quality of which is often compromised by various factors. Therefore, a gas chromatographic method has been developed and validated to confirm the results of an established spectrophotometric method and to determine the concentration of COHb in postmortem samples affected by processes such as putrefaction or thermocoagulation. This method is based on automated headspace analysis of a blood sample treated with a solution of potassium hexacyanoferrate and saponin. It employs a combination of two capillary columns for chromatographic separation, followed by a highly sensitive detection system that incorporates a methanizer to convert carbon monoxide (CO) to methane couple to a flame ionization detector. The percentage of COHb concentration is calculated using the ratio of the analyzed blood to that of fully CO-saturated blood. Careful optimization of the method has reduced the sample requirement to 100 mg while maintaining high sensitivity. Additionally, the sample pretreatment process has been simplified to ensure that the method can be easily integrated into the routine operation of a conventional forensic laboratory. The method demonstrates linearity across a concentration range of 0.1% to 100% COHb. The determined values of limit of detection (<0.01% COHb) and limit of quantification (0.1% COHb) reflect excellent sensitivity. Overall, the validation study confirmed the method for its intended purpose. The method is particularly effective in reliably determining COHb content in putrefied and similarly degraded samples. Its robustness has been further validated through the analysis of dozens of real samples over more than 4 years.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274705","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":"Stability of 22 sedative-type drugs and metabolites in human urine under variable pH, temperature, and freeze-thaw conditions.","authors":"Feng-Shuo Yang, Shu-Huei Jian, Yi-Cheng Lee, Yung-Sheng Lan, Li-Ping Tseng, Yung-Hung Lee, Yi-Chen Chiu, Yi-Ching Lin","doi":"10.1093/jat/bkaf100","DOIUrl":"10.1093/jat/bkaf100","url":null,"abstract":"<p><p>Ensuring analyte stability is essential for accurate forensic and clinical detection of sedative-type drugs. This study systematically evaluated the stability of 22 sedative-type drugs and metabolites in human urine under controlled conditions varying by pH (4.0, 7.0), temperature (25°C, 4°C, -20°C), and freeze-thaw cycles (5 cycles), using a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. While compounds such as midazolam, clobazam, and zolpidem remained highly stable, others-including alprazolam, triazolam, and lorazepam-exhibited notable degradation, particularly under acidic pH and elevated temperature. Flunitrazepam and clonazepam showed distinct degradation with the formation of 7-amino metabolites at neutral pH. Notably, this transformation occurred only in urine and not in phosphate-buffered saline, suggesting a urine-specific mechanism. These findings highlight the importance of compound-specific preservation strategies. In scenarios where analyte identity or sample pH cannot be verified promptly, immediate refrigeration or freezing (ideally at -20°C), along with minimizing freeze-thaw cycles, is strongly recommended to preserve sample integrity and ensure reliable toxicological interpretation.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482118","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":"Systemic organophosphate poisoning in child following anti-lice lotion application.","authors":"Frédéric Aknouche, Romain Magny, Christophe Maruejouls, Claire Trebuchet, Kevin Fargeot, Laureen Thion, Cory Valancony, Florian Scherrer, Nouzzha Djebrani Oussedik, Pascal Kintz, Laurence Labat, Pascal Houzé","doi":"10.1093/jat/bkaf096","DOIUrl":"10.1093/jat/bkaf096","url":null,"abstract":"<p><p>We report a case of systemic organophosphate (OP) poisoning in a young child following the use of a household shampoo containing diazinon. In previous reported cases, diagnosis is typically made rapidly and indirectly through decreased cholinesterase activity and identification of OPs in commercial containers. In our case, however, the diagnosis was significantly delayed due to nonspecific clinical signs and a language barrier between the family and medical staff, resulting in the development of an intermediate syndrome. Initial symptoms included gastrointestinal disturbances, followed several hours later by neurological and respiratory complications. Plasma, urinary, and hair arsenic levels were first investigated due to the use of a product which may contain organometallic copper acetoarsenite complex. All arsenic concentrations were within physiological concentrations. Clinical presentation and biological cholinesterase activity (313 U/L vs. reference 1900-3800 U/L) later supported the diagnosis of OP poisoning. This hypothesis was reinforced by the analysis of the household shampoo indicating the presence of diazinon. Furthermore, despite the delayed diagnosis, non-targeted high-resolution mass spectrometry (LC-HR-MS/MS) identified diazinon in plasma and multiple phase I metabolites, including the specific marker IMPY, in both plasma and urine. Four previously undescribed metabolites and one phase II metabolite, hydroxy-IMPY-glucuronide, were also detected. Pralidoxime methylsulfate (Contrathion™) was administered on day 4, following toxicological confirmation and lack of clinical improvement. Although late, this treatment led to gradual neurological recovery, suggesting possible slow \"aging\" of diazinon-inhibited acetylcholinesterase. Nonetheless, the child developed persistent sequelae including hypotonia, peripheral neuropathies, and respiratory dysfunction consistent with intermediate syndrome. This case highlights the importance of considering OP poisoning even in atypical presentations and illustrates the utility of non-targeted HRMS screening in providing direct evidence of exposure when conventional approaches are inconclusive.</p>","PeriodicalId":14905,"journal":{"name":"Journal of analytical toxicology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345264","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}