Forensic Toxicology最新文献

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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. 池化人肝微粒体酶解∆8-THC- o、∆9-THC- o、11-α-HHC- o、11-β-HHC- o生成∆8-THC、∆9-THC、11-α-HHC、11-β-HHC。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-03-28 DOI: 10.1007/s11419-025-00719-2
Shuangli Zhao, Jorge Carlos Pineda García, Ren-Shi Li, Ruri Kikura-Hanajiri, Yosuke Demizu, Yoshitaka Tanaka, Yuji Ishii
{"title":"Enzymatic hydrolysis of ∆<sup>8</sup>-THC-O, ∆<sup>9</sup>-THC-O, 11-α-HHC-O, and 11-β-HHC-O by pooled human liver microsomes to generate ∆<sup>8</sup>-THC, ∆<sup>9</sup>-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":"https://doi.org/10.1007/s11419-025-00719-2","url":null,"abstract":"<p><strong>Purpose: </strong>In recent years, analogues of ∆<sup>9</sup>-tetrahydrocannabinol (∆<sup>9</sup>-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 ∆<sup>9</sup>-THC, ∆<sup>8</sup>-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 ∆<sup>9</sup>-THC-O, ∆<sup>8</sup>-THC-O, 11-α-HHC-O, and 11-β-HHC-O are enzymatically hydrolyzed with HLM to produce ∆<sup>9</sup>-THC, ∆<sup>8</sup>-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":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","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}
引用次数: 0
Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ9-tetrahydrocannabinol metabolites. 六氢大麻酚代谢物11-no -9-羧基六氢大麻酚外显体的交叉反应性与尿液Δ9-tetrahydrocannabinol代谢物的小组试验
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-03-28 DOI: 10.1007/s11419-025-00717-4
Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata
{"title":"Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ<sup>9</sup>-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":"https://doi.org/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-Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC-COOH), a major urinary metabolite of Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), HHC-COOH may show cross-reactivity in panel tests for urinary Δ<sup>9</sup>-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 Δ<sup>9</sup>-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 Δ<sup>9</sup>-THC metabolites should pay attention to false positives potentially caused by HHC metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","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}
引用次数: 0
Investigation of commercially available recombinant and conventional β-glucuronidases to evaluate the hydrolysis efficiencies against O-glucuronides and N-glucuronides in urinary drug screening. 研究市售重组和常规β-葡萄糖醛酸酶在尿药筛选中对o -葡萄糖醛酸和n -葡萄糖醛酸的水解效率。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-03-05 DOI: 10.1007/s11419-025-00715-6
Akira Namera, Takeshi Saito, Masataka Nagao
{"title":"Investigation of commercially available recombinant and conventional β-glucuronidases to evaluate the hydrolysis efficiencies against O-glucuronides and N-glucuronides in urinary drug screening.","authors":"Akira Namera, Takeshi Saito, Masataka Nagao","doi":"10.1007/s11419-025-00715-6","DOIUrl":"https://doi.org/10.1007/s11419-025-00715-6","url":null,"abstract":"<p><strong>Purpose: </strong>To achieve the rapid analysis of drug metabolites in urine, we examined the differences in the hydrolysis efficiencies against O-glucuronide and N-glucuronide by two commercially available glucuronidases and three commercially available recombinant ones.</p><p><strong>Methods: </strong>The metabolites analyzed included oxazepam-O-glucuronide, amitriptyline-N-glucuronide, and diphenhydramine-N-glucuronide. Hydrolysis was performed using commercially available five enzymes at two different temperatures, and the reaction progress was monitored for up to 360 min. The amount of hydrolyzed product was quantified using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Although no enzyme selectivity was observed for the hydrolysis of O-glucuronide, the hydrolysis efficiency against N-glucuronide varied significantly, depending on the enzyme and reaction temperature. Among the enzymes evaluated, IMCSzyme 3S and the enzyme derived from E. coli demonstrated superior hydrolysis of N-glucuronides under optimal conditions. For IMCS RT, good results were also obtained by adding twice the amount of enzyme specified.</p><p><strong>Conclusions: </strong>Suitable enzymes and hydrolysis conditions were determined for the rapid and systematic screening of drug metabolites in human urine. These findings are expected to streamline the analytical workflow and reduce the need for tedious sample preprocessing.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556243","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}
引用次数: 0
Eleven new metabolites of fluvoxamine detected in the solid tissues and body fluids obtained from a deceased overdosed with fluvoxamine in vivo, and the metabolites in the human liver microsomes in vitro using LC-HR-MS/MS. 利用 LC-HR-MS/MS 技术,在一名服用氟伏沙明过量的死者体内获得的固体组织和体液中检测到氟伏沙明的 11 种新代谢物,并在体外检测到人肝微粒体中的代谢物。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-03-01 DOI: 10.1007/s11419-025-00714-7
Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Kenta Yuyama, Masako Suzuki, Takuya Kitamoto, Minako Kondo, Osamu Suzuki, Koutaro Hasegawa
{"title":"Eleven new metabolites of fluvoxamine detected in the solid tissues and body fluids obtained from a deceased overdosed with fluvoxamine in vivo, and the metabolites in the human liver microsomes in vitro using LC-HR-MS/MS.","authors":"Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Kenta Yuyama, Masako Suzuki, Takuya Kitamoto, Minako Kondo, Osamu Suzuki, Koutaro Hasegawa","doi":"10.1007/s11419-025-00714-7","DOIUrl":"https://doi.org/10.1007/s11419-025-00714-7","url":null,"abstract":"<p><strong>Purpose: </strong>Fluvoxamine (FLV) has been used widely as an antidepressant agent belonging to the group of second-generation selective serotonin reuptake inhibitors. However, only one work on the human metabolism of FLV was reported in 1983, examining a human urine specimen, and tentatively identified nine metabolites. Therefore, in the present work, the metabolites of FLV were examined in the liver, bile, and urine from a human cadaver, and the metabolites produced in the human liver microsomes (HLMs) in vitro were also examined.</p><p><strong>Methods: </strong>Metabolites in each matrix were treated altogether in a tube where impurities had been precipitated using acetonitrile. The identification and tentative quantification of metabolites in human specimens and HLMs were performed using liquid chromatography (LC)-high resolution mass spectrometry (MS), LC-tandem mass spectrometry (MS/MS) and LC-QTRAP- MS/MS.</p><p><strong>Results: </strong>Eleven new metabolites designated as M1 to M11 were detected from human cadaver specimens and HLMs. M1 was produced after acetylation at the terminal NH<sub>2</sub> of FLV and was the most abundant metabolite in the liver and bile, but was the third abundant one in urine. M4 was produced after demethylation at the methoxy moiety of FLV, and was the most abundant metabolite in HLMs.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first report on the existence of eleven new metabolites (M1-M11) of FLV in HLMs, human liver, bile and urine. The present eleven metabolites may be useful for the identification of FLV in human samples both antemortem and postmortem.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536985","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}
引用次数: 0
Analysis of cyanide exposure status in fire-related deaths using a physiologically based pharmacokinetic model. 使用基于生理学的药代动力学模型分析火灾相关死亡中的氰化物暴露状况。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-02-25 DOI: 10.1007/s11419-025-00713-8
Kazuo Harada, Yuri Tokugawa, Kazunari Henmi, Yohei Miyashita, Yuji Sakahashi, Taichi Nishihori, Yukari Sakamoto, Chihpin Yang, Yu Isobe, Kana Sugimoto, Kentaro Nakama, Ryuichi Katada, Hiroshi Matsumoto
{"title":"Analysis of cyanide exposure status in fire-related deaths using a physiologically based pharmacokinetic model.","authors":"Kazuo Harada, Yuri Tokugawa, Kazunari Henmi, Yohei Miyashita, Yuji Sakahashi, Taichi Nishihori, Yukari Sakamoto, Chihpin Yang, Yu Isobe, Kana Sugimoto, Kentaro Nakama, Ryuichi Katada, Hiroshi Matsumoto","doi":"10.1007/s11419-025-00713-8","DOIUrl":"https://doi.org/10.1007/s11419-025-00713-8","url":null,"abstract":"<p><strong>Purpose: </strong>Fire victims often inhale hydrogen cyanide (HCN) gas in addition to carbon monoxide. This study aimed to investigate the current prevalence of HCN inhalation among fire victims and assess the contribution of HCN as a toxic factor in fire-related deaths.</p><p><strong>Methods: </strong>The study included 29 cases of fire-related deaths, where autopsies were conducted at the Department of Legal Medicine, Osaka University, from April 2014 to March 2020. No resuscitation was performed before death was confirmed and blood samples were obtained from both the left and right cardiac chambers. Blood cyanide concentrations were measured. Additionally, a physiologically based pharmacokinetic model, as described by Stamyr et al. (Arch Toxicol 89:1287-1296, 2015), was used to simulate the time course of blood concentration changes for different inhaled HCN concentrations. The inhaled HCN concentration and inhalation time that minimized the difference between the measured and simulated blood concentrations were calculated.</p><p><strong>Results: </strong>Cyanide was detected in the cardiac blood of 76.3% of cases. In all instances, left cardiac blood concentrations were higher than those in the right cardiac blood. The simulations using the physiologically based pharmacokinetic model revealed eight cases where the inhaled HCN concentration exceeded 5000 ppm, with an inhalation time of less than 0.5 min.</p><p><strong>Conclusions: </strong>Many fire victims inhaled HCN gas, and in a few cases, it appears that death occurred rapidly after inhalation of high HCN concentrations. These findings suggest that the contribution of cyanide gas to fire-related deaths warrants closer examination.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491461","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}
引用次数: 0
GC/MS-based quantitative analysis of sulfide ion in whole blood using ethenesulfonyl fluoride as a derivatization reagent. 以乙烯磺酰氟为衍生试剂,气相色谱/质谱法定量分析全血中硫化物离子。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-02-10 DOI: 10.1007/s11419-025-00712-9
Ryosuke Shiraki, Shin Ogawa, Kengo Wakigawa, Hidehiko Okazaki, Akinaga Gohda, Takeshi Mori, Yoshiki Katayama
{"title":"GC/MS-based quantitative analysis of sulfide ion in whole blood using ethenesulfonyl fluoride as a derivatization reagent.","authors":"Ryosuke Shiraki, Shin Ogawa, Kengo Wakigawa, Hidehiko Okazaki, Akinaga Gohda, Takeshi Mori, Yoshiki Katayama","doi":"10.1007/s11419-025-00712-9","DOIUrl":"10.1007/s11419-025-00712-9","url":null,"abstract":"<p><strong>Purpose: </strong>Identification and quantification of sulfide ion in biological samples are required in forensic purpose. Gas chromatography-mass spectrometry (GC/MS) has been used for the analysis of sulfide ion by using derivatization reagents. However, conventional derivatization reagents require special attention for derivatization. To simplify the derivatization protocol, we examined ethenesulfonyl fluoride (ESF) as a derivatizing reagent of sulfide ion.</p><p><strong>Methods: </strong>To 100 μL of whole blood sample containing sulfide ion, 100 μL of boric acid buffer (pH 8.0), 100 μL of acetone solution containing internal standard, 100 μL of acetone solution containing 600 mM concentration of ESF, and 100 μL of hexane were added in a 1.5-mL plastic tube. The mixture was vortexed at room temperature, the tubes were centrifuged, and the organic layer was injected into the GC/MS.</p><p><strong>Results: </strong>ESF exhibited higher reactivity toward sulfide ion than interfering compounds present in whole blood, allowing for selective derivatization. With the optimized protocol, the detection limit for sulfide ion was 0.01 μg/mL. The calibration curve showed good linearity (R<sup>2</sup> = 0.9999) in the range of 0.05-10.0 μg/mL, and the precision (% relative standard deviation) and the accuracy (% bias) were within ± 10% (intra- and inter-day).</p><p><strong>Conclusion: </strong>This GC/MS-based method is a valuable tool for forensic investigations and various analytical fields, offering reliable quantification of sulfide ion in whole blood.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382042","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}
引用次数: 0
Detection and quantification of drugs on banknotes by LC-MS/MS with a fast and non-destructive sample preparation: a comparison of three cities. 快速无损制样的LC-MS/MS检测与定量钞票上的药物:三个城市的比较
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-01-30 DOI: 10.1007/s11419-025-00711-w
Göksun Demirel, Yeter Erol Öztürk, Oya Yeter, Hızır Aslıyüksek
{"title":"Detection and quantification of drugs on banknotes by LC-MS/MS with a fast and non-destructive sample preparation: a comparison of three cities.","authors":"Göksun Demirel, Yeter Erol Öztürk, Oya Yeter, Hızır Aslıyüksek","doi":"10.1007/s11419-025-00711-w","DOIUrl":"https://doi.org/10.1007/s11419-025-00711-w","url":null,"abstract":"<p><strong>Purpose: </strong>The analysis of drug residues on some currencies is well-established in the literature. However, there is no published study describing the presence of drug residues on Turkish paper currency.</p><p><strong>Methods: </strong>This study focused on the analysis of 14 drug residues present on 600 Turkish banknotes collected from three different cities: Ankara, Adana, and Istanbul. The banknotes underwent preparation by a non-destructive and straightforward extraction method using methanol. To investigate the extent of contamination a method was subsequently developed and validated for liquid chromatography triple quadrupole mass spectrometry analysis to detect and quantify the target analytes. The investigated substances included benzoylecgonine, cocaine, heroin, codeine, morphine, 6-monoacetylmorphine (6-AM), amphetamine, methamphetamine, 3,4-methylenedioxy-N-methamphetamine (MDMA), methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (MDMB-4EN-PINACA), N-[1-(aminocarbonyl)-2,2-dimethylpropyl]-1-butyl-1H-indazole-3-carboxamide (ADB-BUTINACA), tetrahydrocannabinol (THC), pregabalin, ketamine, and tramadol.</p><p><strong>Results: </strong>The calculated mean concentrations per note were 475.5 ng cocaine, 660.7 ng methamphetamine, 220.4 ng benzoylecgonine, 36.5 ng ketamine, 46.0 ng amphetamine, 120.6 ng 6-AM, 22.9 ng morphine, 6.3 ng codeine, 107.4 ng THC, 1.3 ng MDMB-4en-PINACA, 1.1 ng ADB-BUTINACA and 65.9 ng MDMA. Our findings indicate that banknotes commonly circulated in the three cities were primarily contaminated with methamphetamine and cocaine.</p><p><strong>Conclusions: </strong>This study highlights the prevalence of drug residues on banknotes and raises concerns about their potential impact. The contamination of Turkish currency with drug residues is a strong indication of the widespread use of banknotes in drug trafficking.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064275","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}
引用次数: 0
Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake. 一次摄入后,毛发中的suvorexant和lemborexant及其分布情况。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1007/s11419-024-00700-5
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
{"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}
引用次数: 0
α-Pyrrolidinooctanophenone facilitates activation of human microglial cells via ROS/STAT3-dependent pathway. α-吡咯烷酮通过 ROS/STAT3 依赖性途径促进人类小胶质细胞的活化
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1007/s11419-024-00708-x
Yuji Sakai, Junta Hattori, Yoshifumi Morikawa, Toshihiro Matsumura, Shunsuke Jimbo, Koichi Suenami, Tomohiro Takayama, Atsushi Nagai, Tomomi Michiue, Akira Ikari, Toshiyuki Matsunaga
{"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}
引用次数: 0
Recent advances in electrochemical detection of common azo dyes. 常见偶氮染料电化学检测的最新进展。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-01-01 Epub Date: 2024-08-02 DOI: 10.1007/s11419-024-00696-y
Sumi Sundaresan, Vijendran Vijaikanth
{"title":"Recent advances in electrochemical detection of common azo dyes.","authors":"Sumi Sundaresan, Vijendran Vijaikanth","doi":"10.1007/s11419-024-00696-y","DOIUrl":"10.1007/s11419-024-00696-y","url":null,"abstract":"<p><strong>Purpose: </strong>Food forensics is an emerging field and the initial part of this review showcases the toxic effects and the instrumental methods applied for the detection of the most commonly used azo dyes. Electrochemical detection has a lot of advantages and hence the significance of the most important techniques used in the electrochemical detection is discussed. The major part of this review highlights the surface modified electrodes, utilized for the detection of the most important azo dyes to achieve low detection limit (LOD).</p><p><strong>Methods: </strong>A thorough literature study was conducted using scopus, science direct and other scientific databases using specific keywords such as toxic azo dyes, electrochemical detection, modified electrodes, LOD etc. The recent references in this field have been included.</p><p><strong>Results: </strong>From the published literature, it is observed that with the growing interests in the field of electrochemical techniques, a lot of importance have been given in the area of modifying the working electrodes. The results unambiguously show that the modified electrodes outperform bare electrodes and offer a lower LOD value.</p><p><strong>Conclusion: </strong>According to the literature reports it can be concluded that, compared to other detection methods, electrochemical techniques are much dependable and reproducible. The fabrication of the electrode material with the appropriate modifications is the main factor that influences the sensitivity. Electrochemical sensors can be designed to be more sensitive, more reliable, and less expensive. These sensors can be effectively used by toxicologists to detect trace amounts of harmful dyes in food samples.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"1-21"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874592","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}
引用次数: 0
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