Forensic Toxicology最新文献

{"title":"Identification of two lysergic acid diethylamide analogs, 1-(3-(trimethylsilyl) propionyl) lysergic acid diethylamide (1S-LSD) and 1-(2-thienoyl)-6-allyl-nor-d-lysergic acid diethylamide (1T-AL-LAD), in paper sheet products distributed on the internet.","authors":"Rie Tanaka, Maiko Kawamura, Michiho Ito, Ruri Kikura-Hanajiri","doi":"10.1007/s11419-025-00718-3","DOIUrl":"https://doi.org/10.1007/s11419-025-00718-3","url":null,"abstract":"<p><strong>Purpose: </strong>Recently, numerous lysergic acid diethylamide (LSD) analogs have emerged as designer drugs globally. These compounds are mainly distributed as sheet products. In this study, two new LSD analogs were identified from sheet products.</p><p><strong>Methods: </strong>The structures of the compounds were determined by gas chromatography-mass spectrometry, liquid chromatography-photodiode array-mass spectrometry, liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance (NMR) measurement.</p><p><strong>Results: </strong>From the NMR analysis, two compounds in the products were identified as N,N-diethyl-7-methyl-4-(3-(trimethylsilyl)propanoyl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1S-LSD) and 7-allyl-N,N-diethyl-4-(thiophene-2-carbonyl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1T-AL-LAD). In the product where 1S-LSD was detected, the presence of a trace amount of iso-1S-LSD, a C8-epimerization product of 1S-LSD, was suggested.</p><p><strong>Conclusions: </strong>This paper is the first to report the detection of 1S-LSD and 1T-AL-LAD in sheet products in Japan. Notably, the metabolic pathways and biological activities of 1S-LSD and 1T-AL-LAD are not explored. The possibility of the in vivo deacylation and conversion of the compoundsinto LSD or AL-LAD should be further investigated.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778992","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":"Beware of misattributing 'modafinil' in diphenhydramine-positive cases.","authors":"Karolina Nowak, Marcin Zawadzki, Paweł Szpot","doi":"10.1007/s11419-025-00716-5","DOIUrl":"https://doi.org/10.1007/s11419-025-00716-5","url":null,"abstract":"<p><strong>Purpose: </strong>Diphenhydramine is an antihistaminic agent available in numerous over-the-counter preparations, while modafinil is a wakefulness-promoting agent, available only by prescription, but also used recreationally, when purchased from the black market. Structurally, both substances belong to the class of so-called benzhydryl compounds, which can complicate their proper differentiation. The authors point out the possibility of misattributing modafinil in diphenhydramine-positive cases due to the likely coelution of nordiphenhydramine and modafinil.</p><p><strong>Methods: </strong>Post-mortem blood and vitreous humor samples were subjected to liquid-liquid extraction using ethyl acetate in an alkaline environment (pH = 9), followed by a detailed toxicological analysis utilizing ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.</p><p><strong>Results: </strong>Through the application of full scan mode, multiple reaction monitoring (MRM), and product ion scan mode, the presence of modafinil was excluded in diphenhydramine-positive biological matrices (blood and vitreous humor).</p><p><strong>Conclusions: </strong>In the analysis of benzhydryl compounds, particular caution should be exercised, with each case verified by comparison with a certified analytical standard, and, where possible, by detecting the metabolites of these compounds.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751937","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":"https://doi.org/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":""},"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}

{"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":"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-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":""},"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}

{"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}

{"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 NH₂ 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}

{"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}

{"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 (R² = 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}

{"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}

{"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}