Forensic Toxicology最新文献

{"title":"Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ⁹-tetrahydrocannabinol metabolites.","authors":"Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-025-00717-4","DOIUrl":"10.1007/s11419-025-00717-4","url":null,"abstract":"<p><strong>Purpose: </strong>The epimers of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) have been identified as metabolites of hexahydrocannabinol (HHC) in human urine. Owing to the similarity of chemical structures to 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (Δ⁹-THC-COOH), a major urinary metabolite of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), HHC-COOH may show cross-reactivity in panel tests for urinary Δ⁹-THC metabolites. The authors have evaluated the cross-reactivity of HHC-COOH epimers in three commercial panel tests.</p><p><strong>Methods: </strong>Human urine spiked with 9α- and 9β-HHC-COOH (final concentrations: 20-500 ng/mL) was subjected to three panel tests (Driven Flow THC L50, IVeX-Screen THC L50-S, and AccuSign THC) with a nominal cutoff concentration of 50 ng/mL for Δ⁹-THC-COOH. Additionally, an intact urine sample from an alleged HHC user was used.</p><p><strong>Results: </strong>The lowest concentrations judged as positive were 100-500 ng/mL for 9α-HHC-COOH and 50-100 ng/mL for 9β-HHC-COOH. Intact urine samples from an alleged HHC user, whose 9α-/9β-HHC-COOH concentrations (ng/mL) were < 4.0/25.5 before alkaline hydrolysis and 13.4/132.2 after alkaline hydrolysis, were positive for all three panel tests.</p><p><strong>Conclusions: </strong>Both epimers of HHC-COOH showed cross-reactivity in three panel tests. The reactivity of 9β-HHC-COOH was found to be higher than that of 9α-HHC-COOH. The urine test results from the alleged HHC user suggested that the acyl glucuronides of HHC-COOH also exhibited cross-reactivity. Users of panel tests for urinary Δ⁹-THC metabolites should pay attention to false positives potentially caused by HHC metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"365-369"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic hydrolysis of ∆⁸-THC-O, ∆⁹-THC-O, 11-α-HHC-O, and 11-β-HHC-O by pooled human liver microsomes to generate ∆⁸-THC, ∆⁹-THC, 11-α-HHC, and 11-β-HHC.","authors":"Shuangli Zhao, Jorge Carlos Pineda García, Ren-Shi Li, Ruri Kikura-Hanajiri, Yosuke Demizu, Yoshitaka Tanaka, Yuji Ishii","doi":"10.1007/s11419-025-00719-2","DOIUrl":"10.1007/s11419-025-00719-2","url":null,"abstract":"<p><strong>Purpose: </strong>In recent years, analogues of ∆⁹-tetrahydrocannabinol (∆⁹-THC) have been widely distributed in Japan via the internet. Hexahydrocannabinol (HHC), synthesized by reducing THC, was controlled as a designated substance under the Pharmaceutical and Medical Device Act in Japan in 2022. However, other semi-synthetic cannabinoids, such as acetyl derivatives of THC and HHC, appeared soon. Herein, we examined whether the enzymatic hydrolysis of acetylated forms of ∆⁹-THC, ∆⁸-THC 11-α-HHC, and 11-β-HHC by human liver microsomes (HLM) occurs.</p><p><strong>Methods: </strong>The hydrolysis reaction was accomplished with HLM. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine products. Recombinant enzymes carboxylesterase 1C (CES1c), carboxylesterase 2 (CES2), and carboxylesterase inhibitor bis-(4-nitrophenyl) phosphate (BNPP) were used to clarify the principal hydrolysis enzymes for acetylated cannabinoids.</p><p><strong>Results: </strong>The acetylated form underwent hydrolysis with HLM time-dependently, with almost no acetylated product remaining after 60 min. Furthermore, results from LC-MS showed that only the deacetylated form was present after hydrolysis. Although hydrolysis did not occur when HLM was pre-incubated with the carboxylesterase inhibitor BNPP, it was observed when CES1c or CES2 was used for in vitro experiments.</p><p><strong>Conclusion: </strong>This is the first time that it is elucidated that ∆⁹-THC-O, ∆⁸-THC-O, 11-α-HHC-O, and 11-β-HHC-O are enzymatically hydrolyzed with HLM to produce ∆⁹-THC, ∆⁸-THC, 11-α-HHC, and 11-β-HHC, respectively. Our results also support that CES1c and CES2 were the main enzymes involved in the hydrolysis of the acetylated cannabinoids. This study provides scientific support for the metabolism of newly regulated acetylated cannabinoids to cause the parent compound in vivo.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"256-265"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-consensual administration of mifepristone for hidden abortion: a rare case of drug-facilitated crime.","authors":"Laurie Gheddar, Audrey Farrugia, Jean-Sébastien Raul, Pascal Kintz","doi":"10.1007/s11419-025-00723-6","DOIUrl":"10.1007/s11419-025-00723-6","url":null,"abstract":"<p><strong>Purpose: </strong>In this paper, the authors report a hidden administration of mifepristone, an antiprogestogen used in abortion procedure, by the boyfriend of a pregnant woman. After drinking an iced tea, the woman experienced pelvic cramps and then expulsed products of conception. Due to conflicts in the couple, she suspected a surreptitious administration of an abortion medicine and reported the fact to the police.</p><p><strong>Methods: </strong>Urine was collected 3 days after the event, while a strand of head hair was collected 1 month later. Urine and hair samples were tested for mifepristone using a liquid chromatography system coupled to tandem mass spectrometry. The limits of detection and quantification were 0.05 and 0.1 ng/mL for urine and 0.5 and 1 pg/mg for hair, respectively.</p><p><strong>Results: </strong>Urine and the hair segment corresponding to the period of the event were positive for mifepristone at 0.4 ng/mL and 1.4 pg/mg, respectively.</p><p><strong>Conclusion: </strong>The presence of mifepristone in both biological specimens demonstrates that the woman was exposed to the drug at the period of the event. The findings of this case make a valuable contribution to the literature, addressing an important gap regarding the concentrations found in biological matrices. There is a few data available in the literature, and these results help to expand knowledge on the subject.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"395-399"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and subacute cardiovascular effects of synthetic cannabinoid JWH-018 in rat.","authors":"Onural Ozhan, Necip Ermis, Osman Celbis, Emine Samdanci, Semih Petekkaya, Mucahit Oruc, Ozcan Soylu, Pelin Koparir, Ahmet Acet, Hakan Parlakpinar","doi":"10.1007/s11419-025-00720-9","DOIUrl":"10.1007/s11419-025-00720-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the cardiovascular effects of the synthetic cannabinoid naphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-018) in rats. The research aims to evaluate the pharmacologic, cardiologic, biochemical, and histopathological effects of acute and subacute administration at low and high doses. The primary research question is how JWH-018 impacts heart function, blood pressure, ECG patterns, and cardiac tissue integrity.</p><p><strong>Methods: </strong>Wistar albino rats were divided into five groups: control, acute low-dose (ALD, 0.5 mg/kg), acute high-dose (AHD, 5 mg/kg), subacute low-dose (SALD, 0.5 mg/kg for 14 days), and subacute high-dose (SAHD, 5 mg/kg for 14 days). Cardiovascular effects were assessed using echocardiography, hemodynamic and ECG analysis, histopathology, biochemical markers, and LC-MS/MS quantification of JWH-018 and its metabolites in heart tissue.</p><p><strong>Results: </strong>Acute high-dose JWH-018 caused bradycardia and hypotension, while subacute high-dose increased heart rate but continued to lower blood pressure. JWH-018 induced cardiac arrhythmias, conduction blocks, and ischemic ECG changes, with prolonged QT intervals in subacute high-dose rats. Histopathological findings revealed myocardial infarction-like features, including contraction bands and ischemic damage, particularly in subacute groups. Elevated pro-BNP and triglycerides indicated cardiac stress and metabolic effects. JWH-018 and its metabolites were detected in heart tissue, primarily in high-dose groups.</p><p><strong>Conclusions: </strong>JWH-018 has significant cardiovascular risks, causing heart rate dysregulation, hypotension, arrhythmias, and ischemic damage. These effects depend on dose and duration. The study highlights the potential dangers of synthetic cannabinoids, emphasizing that they should not be considered safe alternatives to natural cannabis.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"266-279"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple method for the determination of stimulant substances in postmortem blood: development, validation, and application in nearly 1000 forensic cases.","authors":"Letícia Birk, Bruno Pereira Dos Santos, Daniela Souza Ossanes, Patrícia de Souza Schwarz, Mariana Lopes Mesquita, Sarah Eller, Tiago Franco de Oliveira","doi":"10.1007/s11419-025-00725-4","DOIUrl":"10.1007/s11419-025-00725-4","url":null,"abstract":"<p><strong>Purpose: </strong>Toxicological analyses of postmortem blood samples are essential to elucidate forensic cases involving toxic agents, such as illicit drugs. A simple method for determining stimulant substances in postmortem blood samples through protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and applied in nearly 1000 samples from Brazilian forensic cases.</p><p><strong>Methods: </strong>For sample preparation, 100 µL of postmortem blood was precipitated using acetonitrile. The supernatant was analyzed via LC-MS/MS system for sixteen substances, including amphetamine, benzoylecgonine, cocaethylene, cocaine, diethylpropion, dimethyltryptamine, ecgonine methyl ester (EME), ephedrine, fenproporex, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, 3,4-methylenedioxymethamphetamine, methamphetamine, methylphenidate, phenylephrine, and sibutramine. The method was validated following the parameters established by the ANSI/ASB Standard 036 Guideline. After validation, a total of 971 postmortem blood samples were analyzed.</p><p><strong>Results: </strong>The lower limits of quantification varied from 5 to 20 ng/mL, with all substances demonstrating linearity up to 1000 ng/mL. The method exhibited maximum precision values of 19.3%, while the bias ranged from - 15.4 to + 4.3%. A significant matrix effect was observed only for EME and phenylephrine. Approximately 20.1% of the analyzed samples tested positive for at least one substance, and 12 out of the 16 target analytes were detected. The most prevalent substances identified were benzoylecgonine (17.8%), ecgonine methyl ester (13.9%), and cocaine (13.0%).</p><p><strong>Conclusions: </strong>A rapid and straightforward LC-MS/MS method for the quantitative analysis of drugs in postmortem blood was validated and successfully applied to nearly 1000 postmortem blood samples.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"400-409"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary excretion profiles of the orexin receptor antagonist suvorexant and its metabolites.","authors":"Misato Wada, Hiroe Kamata, Noriaki Shima, Atsushi Nitta, Hidenao Kakehashi, Shihoko Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Hiroshi Nishioka","doi":"10.1007/s11419-024-00706-z","DOIUrl":"10.1007/s11419-024-00706-z","url":null,"abstract":"<p><strong>Purpose: </strong>Suvorexant is an orexin receptor antagonist used in the treatment of insomnia. In this study, we investigated the urinary excretion profiles of suvorexant and its major metabolites, including conjugates, to obtain fundamental information for proving exposure to suvorexant in criminal cases.</p><p><strong>Methods: </strong>Urine specimens were collected from three subjects for maximum 168 h after a single oral ingestion of suvorexant (10 mg), and suvorexant and its metabolites in urine were determined using liquid chromatography-tandem mass spectrometry with a C18 semi-micro column.</p><p><strong>Results: </strong>The carboxylic and hydroxy metabolites (M4 and M9) were identified with authentic standards synthesized in our laboratory, and their glucuronides and other hydroxy metabolites (M8 and M10) were tentatively detected based on measured exact masses and product ion spectra of them. Suvorexant, M4 and M9 would be detectable for 20-34 h, 6-7 days and 42-61 h after intake, respectively. The quantitative results demonstrated that the molar ratios of accumulated amounts of M4 and M9 including their glucuronides excreted in urine to dose ranged about 2.6-6.2% and 0.37-0.51%, respectively, while that of the unchanged parent was much lower (0.011-0.013%). The ratios of the amount of glucuronide to the total amount of M4 and M9 excreted in urine was less than 10% and approximately 90%, respectively.</p><p><strong>Conclusions: </strong>The urinary excretion profiles indicated that M4 and M9 would be effective indicators for proving suvorexant intake, and M4 could be detected until one week after intake even without enzymatic hydrolysis (limit of detection: 0.05 ng/mL).</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"179-189"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of the transient matrix effect for determination of anabolic-androgenic steroids in biological samples by GC-MS/MS.","authors":"Michal P Dybowski, Krystian Siwek","doi":"10.1007/s11419-025-00731-6","DOIUrl":"https://doi.org/10.1007/s11419-025-00731-6","url":null,"abstract":"<p><strong>Purpose: </strong>Anabolic-androgenic steroids (AAS) enhance athletic performance, giving athletes an unfair advantage and disrupting fair competition. Banned in sports and listed by World Anti-Doping Agency, they require precise detection. This study aimed to develop a method using the transient matrix effect to improve AAS identification in biological samples.</p><p><strong>Methods: </strong>Gas chromatography-tandem mass spectrometry (GC-MS/MS) method for determination of AAS samples was developed and validated. Biological samples were prepared using the QuEChERS technique.</p><p><strong>Results: </strong>The optimised and validated method enhances AAS signals using high-boiling protectants. It ensures good linearity, low detection limits, and reliable precision. Optimal QuEChERS extraction and multiple reaction monitoring transitions in GC-MS/MS were evaluated, confirming applicability with blood plasma samples. The addition of a protectant to the analysed sample results in several notable effects. High-boiling protectants, such as polyethylene glycol (PEG-400), tetradecanoic acid (C14-COOH), n-tetradecylalcohol (C14-OH), and n-tetradecylamine (C14-NH₂), significantly enhance AAS's signal in blood plasma. This enhancement, however, is accompanied by a transient matrix effect induced by the protectants. PEG-400 produced the most substantial signal increase, with the response for nandrolone rising by as much as 912%.</p><p><strong>Conclusions: </strong>The results demonstrate the potential offered by the utilisation of PEG-400 as a protectant to generate a transient matrix effect. The outcome of this process is an increased analytical signal from AAS in blood plasma, enabling their identification even at trace concentrations. The methodology developed and applied during the study can be used to reduce the detection limit of steroids and thus improve antidoping measures in sport.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative analysis of ethylene glycol in human serum by liquid chromatography-tandem mass spectrometry with p-toluenesulfonyl isocyanate derivatization.","authors":"Shin Ogawa, Ryosuke Shiraki, Kengo Wakigawa, Hidehiko Okazaki, Akira Tsujita, Akinaga Gohda, Toshiro Matsui","doi":"10.1007/s11419-025-00729-0","DOIUrl":"https://doi.org/10.1007/s11419-025-00729-0","url":null,"abstract":"<p><strong>Purpose: </strong>Ethylene glycol (EG) is a typical antifreeze compound and a significant analyte in forensic toxicology. Current EG analytical method for biological samples in forensic toxicology employ liquid chromatography-tandem mass spectrometry (LC-MS/MS), however, they exhibit low sensitivity and reliability. Therefore, in this study, we aimed to establish a highly sensitive, selective, and reliable EG assay system for human serum analysis using a hydroxyl derivatization-aided LC-MS/MS technique.</p><p><strong>Methods: </strong>p-Toluenesulfonyl isocyanate (PTSI) was applied for precolumn derivatization of EG in human serum, to enhance the sensitivity of LC-MS/MS for EG detection.</p><p><strong>Results: </strong>The optimal derivatization conditions were 200 µL/mL PTSI in acetonitrile at 25 °C for 10 min. A highly sensitive and reliable LC-MS/MS detection of EG in human serum was achieved, with the calibration curve exhibiting a good linearity (r > 0.999, 10-1000 µg/mL of EG). The proposed PTSI-derivatization-LC-MS/MS method exhibited high reliability (1.4-1.8%) for the intra-day and inter-day repeatability (%RSD), and accuracy (96.7-102.4%), with the limits of detection and quantification in human serum being 0.023 µg/mL (S/N = 3) and 0.077 µg/mL (S/N = 10), respectively.</p><p><strong>Conclusions: </strong>A novel PTSI derivatization-aided LC-MS/MS method was developed, offering a highly sensitive, selective, and reliable analytical tool for EG quantification in human serum for forensic toxicology applications.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake.","authors":"Atsushi Nitta, Noriaki Shima, Hiroe Kamata, Misato Wada, Kengo Matsumoto, Hidenao Kakehashi, Shihoko Nakano-Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Takako Sato, Hiroshi Nishioka","doi":"10.1007/s11419-024-00700-5","DOIUrl":"10.1007/s11419-024-00700-5","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration.</p><p><strong>Methods: </strong>Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair.</p><p><strong>Results: </strong>Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study.</p><p><strong>Conclusions: </strong>This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"97-107"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Pyrrolidinooctanophenone facilitates activation of human microglial cells via ROS/STAT3-dependent pathway.","authors":"Yuji Sakai, Junta Hattori, Yoshifumi Morikawa, Toshihiro Matsumura, Shunsuke Jimbo, Koichi Suenami, Tomohiro Takayama, Atsushi Nagai, Tomomi Michiue, Akira Ikari, Toshiyuki Matsunaga","doi":"10.1007/s11419-024-00708-x","DOIUrl":"10.1007/s11419-024-00708-x","url":null,"abstract":"<p><strong>Purpose: </strong>Pyrrolidinophenone derivatives (PPs) are amphetamine-like designer drugs containing a pyrrolidine ring, and their adverse effects resemble those of methamphetamine (METH). Microglial activation has been recently suggested as a key event in eliciting the adverse effects against dysfunction of the central nervous system. The aim of this study is to clarify the mechanisms of microglial activation induced by PPs.</p><p><strong>Methods: </strong>We employed the human microglial cell line HMC3 to assess microglial activation induced by PPs and evaluated the capacities for proliferation and interleukin-6 (IL-6) production that are characteristic features of the activation events.</p><p><strong>Results: </strong>The WST-1 assay indicated that viability of HMC3 cells was increased by treatment with sublethal concentrations (5-20 µM) of α-pyrrolidinooctanophenone (α-POP), a highly lipophilic PP, whereas it was decreased by treatment with concentrations above 40 µM. Treatment with sublethal α-POP concentrations up-regulated the expression and secretion of IL-6. Additionally, α-POP-induced increase in cell viability was restored by pretreating with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, and stattic, an inhibitor of signal transducer and activator of transcription 3 (STAT3), respectively, suggesting that activation of the ROS/STAT3 pathway is involved in the α-POP-induced activation of HMC3 cells. The increases in cell viability were also observed in HMC3 cells treated with other α-POP derivatives and METH.</p><p><strong>Conclusions: </strong>These results suggest that enhanced productions of ROS and IL-6 are also involved in microglial activation by drug treatment and that HMC3 cell-based system is available to evaluate accurately the microglial activation induced by abused drugs.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"142-154"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}