Forensic Toxicology最新文献

{"title":"The determination of the novel insomnia medication lemborexant using a validated liquid chromatography-tandem mass spectrometry method, and its quantitation in clinical and forensic samples.","authors":"Brian Waters, Masato Masuda, Aya Matsusue, Masayuki Kashiwagi, Hikaru Hori, Kazuya Ikematsu, Shin-Ichi Kubo","doi":"10.1007/s11419-025-00733-4","DOIUrl":"https://doi.org/10.1007/s11419-025-00733-4","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to detail the identification, confirmation, and quantitation of lemborexant from clinical and postmortem specimens using a validated LC-MS/MS method. Additionally, it investigates the tissue distribution of lemborexant in several postmortem cases.</p><p><strong>Methods: </strong>Lemborexant was isolated from the plasma of hospital patients or the postmortem specimens of forensic autopsy cases. Extraction from 0.1 mL or 0.1 g of sample was achieved by a modified QuEChERS protocol. The analysis was performed by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). The quantitation method was validated in whole blood using internationally accepted parameters based on ANSI/ASB Standard 036. A total of 8 clinical samples and 13 forensic autopsy cases were analyzed by the validated method.</p><p><strong>Results: </strong>In clinical cases, lemborexant concentrations in plasma ranged from 2.7 to 225 ng/mL. Lemborexant concentrations in the blood of forensic autopsy cases ranged from below the lower limit of quantitation (2 ng/mL) to 276 ng/mL. The highest postmortem concentrations were found in liver, adipose tissue, pancreas, and kidney. The method demonstrated high recovery rates and precision, with no significant matrix effects or interferences from other drugs.</p><p><strong>Conclusions: </strong>The validated LC-MS/MS method proved effective for detecting and quantifying lemborexant in both clinical and forensic autopsy samples. The study highlights the importance of monitoring lemborexant and other dual orexin receptor antagonists (DORAs) in forensic investigations to understand their pharmacokinetics and potential toxicological effects.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648972","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":"Identification of two novel imidazole-derived GABA agonists butomidate and tf-etomidate in e-cigarette liquids.","authors":"Xiaolong Zhang, Yaqing Li, Jinlei Liu, Ziyi Pan, Yuxuan Chen, Mengchao Wang, Yinyin Dai, Kundi Zhao, Jie Gu, Huimin Zhang, Shengnan Zhang, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-025-00732-5","DOIUrl":"https://doi.org/10.1007/s11419-025-00732-5","url":null,"abstract":"<p><strong>Purpose: </strong>Recently, a number of abuse and intoxication cases involving imidazole-derived GABA agonists etomidate and its analogs have been reported in China. During our recent screening of e-cigarette liquids, we encountered two novel etomidate analogs that have not previously been reported. This study aims to present the analytical procedures used to identify these compounds, along with detailed data obtained under various instrumental conditions.</p><p><strong>Methods: </strong>Identification of the substances of concern was carried out using various instruments, including gas chromatography-mass spectrometry (GC-MS), headspace gas chromatography (HS-GC), liquid chromatography-high-resolution mass spectrometry (LC-HRMS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>Analysis of the e-cigarette samples of concern using GC-MS, LC-HRMS, and LC-MS/MS yielded mass spectra, product ion mass spectra, and high-resolution mass spectra, which allowed structural elucidation. HS-GC analysis of hydrolyzed alcohols provided further insights into the substituent groups linked to imidazole core. Finally, the compounds were identified as butomidate and trifluoro-etomidate (tf-etomidate) through comparison with reference standards. Product ion mass spectra of the reference standards at various collision energies were obtained by LC-MS/MS, which also matched those of the target compounds.</p><p><strong>Conclusion: </strong>This study demonstrated the ion spectra of butomidate, sec-butomidate and tf-etomidate as obtained by GC-MS, and their product ion spectra under varying collision energies by LC-MS/MS. These findings enabled the identification of the compounds in the dubious e-cigarette liquids. To our knowledge, this is the first report detailing qualitative procedures and associated instrumental data for the identification of butomidate and tf-etomidate.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607898","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":"Hair testing for investigating intake and use history of hypnotics in the forensic field.","authors":"Noriaki Shima, Munehiro Katagi, Takako Sato","doi":"10.1007/s11419-025-00730-7","DOIUrl":"https://doi.org/10.1007/s11419-025-00730-7","url":null,"abstract":"<p><strong>Purpose: </strong>Hair testing for drugs has been used extensively in the forensic field since the 1990s, primarily in cases involving abused drugs such as methamphetamine and cocaine. Since the 2010s, its scope has expanded to include the detection of single dose of hypnotics, aiding in the investigation of serious crimes. This review presents essential knowledge for hair testing and the currently recommended analytical procedures and forensic applications.</p><p><strong>Methods: </strong>A review of literature from the 1990s to the 2020s was conducted, focusing on analytical methods for detecting drugs in hair, drug concentrations in hair, and drug incorporation pathways.</p><p><strong>Results: </strong>The characteristics of hair as a biological specimen include a longer detection window than other matrices such as urine and blood, as ingested drugs remain stable in hair over time. Significant differences in drug concentrations in hair are observed among substances, with several hypnotics, such as triazolam, having extremely low concentrations. Drugs are incorporated into hair primarily through two main pathways (the hair bulb and the upper dermis zone), with the dominant pathway depending on the drug's properties. In addition, hair dyeing and subsequent exposure to aqueous environments (e.g., daily hair washing) can significantly influence drug concentrations and their distribution patterns (concentration and hair region). These factors must be carefully considered in hair testing.</p><p><strong>Conclusions: </strong>Hair testing is an effective means for proving drug intake and estimating use history, particularly in cases where there is a delay in reporting the incident. The interpretation of results must account for various factors, such as the chemical structures of drugs, incorporation pathways, and hair dyeing.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575162","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":"Development of a novel Δ⁹-THC-specific color test reagent.","authors":"Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-025-00727-2","DOIUrl":"10.1007/s11419-025-00727-2","url":null,"abstract":"<p><strong>Purpose: </strong>Existing on-site color tests for cannabis (e.g., rapid Duquénois-Levine reagent, 4-aminophenol reagent) have insufficient specificity, especially in the point of distinguishing between Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and the other cannabinoids. We developed a novel Δ⁹-THC-specific color test reagent.</p><p><strong>Methods: </strong>Cannabinoid standards were dissolved in 0.5 mL of a 2-hydroxybenzaldehyde solution in acetonitrile (2 g/100 mL) in a glass test tube (solution A). Herbal samples (approximately 10 mg) were extracted using 0.5 mL of the 2-hydroxybenzaldehyde solution in a plastic homogenization vessel. The extract was poured into a glass test tube through a filter cap (solution B). Solutions A and B were mixed with hydrochloric acid (0.5 mL) and allowed to react for 30 s, after which the mixture was extracted with chloroform (1 mL).</p><p><strong>Results: </strong>When observing the lower layer after the chloroform extraction, Δ⁹-THC and cannabidiol (CBD) exhibited bluish and orangish colors, respectively. In contrast, cannabinol (CBN) did not show any color. The performance of the reagent was evaluated using dried herbal cannabis (n = 58) and other herbal materials (n = 13), including CBD- and CBN-supplemented herbal materials (each n = 2). Only cannabis samples with Δ⁹-THC levels ≥ 0.14% exhibited a bluish or greenish-blue color.</p><p><strong>Conclusions: </strong>The newly developed reagent shows good specificity for Δ⁹-THC. The new reagent has the potential to replace existing on-site color tests.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"318-332"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101647","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":"Method for determination of cytisine in post-mortem biological matrices and its application to two forensic cases.","authors":"Karolina Nowak, Paweł Szpot, Marcin Zawadzki, Agnieszka Chłopaś-Konowałek","doi":"10.1007/s11419-024-00710-3","DOIUrl":"10.1007/s11419-024-00710-3","url":null,"abstract":"<p><strong>Purpose: </strong>Cytisine is the active ingredient in preparations used for smoking cessation. Its popularity is attributed to its low cost, efficacy, and low incidence of adverse effects. Additionally, its easy over-the-counter availability is also significant. This accessibility makes it a potential substance for use in suicidal attempts. The aim of this study was to develop a method for the determination of cytisine in biological material for use in clinical and forensic toxicology, and to apply this method in authentic cases.</p><p><strong>Methods: </strong>Biological samples were subjected to liquid-liquid extraction using cytisine-d₄ as an internal standard. Analyses were performed using a Hydrophilic Interaction Liquid Chromatography (HILIC) column with the technique of ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry.</p><p><strong>Results: </strong>For both matrices (blood and urine), the linear concentration range was 5-1000 ng/mL. The method met all validation requirements. The concentration of cytisine in a man taking it for smoking cessation in post-mortem materials was 21.4 ng/mL in blood, 958.9 ng/mL in urine, ca. 30 ng/mL in vitreous humor, and ca. 40 ng/mL in bile. In contrast, for a man with cytisine intoxication, the concentration was 174.6 ng/mL in blood and > 10,000 ng/mL in urine. In both cases, no N-methylcytisine was detected.</p><p><strong>Conclusions: </strong>The developed method can be used for the determination of cytisine in post-mortem biological matrices as well as for clinical purpose. We presented the concentrations of cytisine in the post-mortem biological samples of a man taking cytisine for smoking cessation and of a man with suicidal cytisine poisoning.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"385-394"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853535","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":"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":"217-225"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241196/pdf/","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":"OA","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":"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":"235-246"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","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":"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":"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":"370-376"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","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":"Preparation of highly concentrated extracts from large volume of urine as the first step in detecting trace amounts of hypnotics in urine collected in drug-facilitated crime cases.","authors":"Kenji Kuwayama, Hajime Miyaguchi, Tatsuyuki Kanamori, Kenji Tsujikawa, Tadashi Yamamuro, Hiroki Segawa, Yuki Okada, Yuko T Iwata","doi":"10.1007/s11419-025-00722-7","DOIUrl":"10.1007/s11419-025-00722-7","url":null,"abstract":"<p><strong>Purpose: </strong>Detecting hypnotics in victim urine samples collected several days after drug-facilitated crime (DFC) is challenging because most of the drugs have already been excreted. In this study, a sample preparation method was developed for extracting trace amounts of hypnotics using most of the urine excreted at one sampling time (100 mL), and large amounts of matrices were efficiently removed.</p><p><strong>Methods: </strong>Etizolam, midazolam, ramelteon, and their metabolites were used as the target compounds. As the first step in decreasing the sample volume, solid-phase extraction using various sorbents was examined. The effects of additional clean-up columns (alumina, graphite, anion exchanger, etc.) on the removal of urine matrices were also examined. The pretreatment of 0.1-mL urine using a simple extraction column, specialized for small-scale urinalysis (Isolute Hydro DME +), was used as the reference method. The feasibility of drug detection in 100-mL urine was evaluated by comparison with a reference method.</p><p><strong>Results: </strong>All analytes in 100-mL urine were most effectively adsorbed on a sorbent with octadecyl-bonded polymer and eluted with less than 2 mL of acetonitrile. A multilayer clean-up column consisting of alumina, octadecyl-bonded silica, and anion exchangers was effective in removing the matrices. α-Hydroxymidazolam was detected in 100 mL of urine that was collected 5 days after midazolam administration, but was undetected using the reference method.</p><p><strong>Conclusions: </strong>This preparation method for 100-mL urine is useful as the first extraction step in detecting trace amounts of hypnotics in victim urine collected late after DFC.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"294-309"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981916","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":"Identification of a novel imidazole-derived GABA agonist isopropoxate: simultaneous detection and quantification of imidazole-derived analogs from human hairs in abused cases by LC-MS/MS.","authors":"Xiaolong Zhang, Yuxuan Chen, Jinlei Liu, Mengchao Wang, Yinyin Dai, Kundi Zhao, Jie Gu, Huimin Zhang, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-024-00707-y","DOIUrl":"10.1007/s11419-024-00707-y","url":null,"abstract":"<p><strong>Purpose: </strong>Distribution and abuse of imidazole-derived γ-aminobutyric acid (GABA) agonists, such as etomidate and metomidate, and their analogs have been encountered frequently especially in China. The aim of this study was to identify etomidate, metomidate, propoxate, and isopropoxate more accurately by establishing a gas chromatography-mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS) method and applying it to real forensic cases.</p><p><strong>Methods: </strong>One mg of the seized powder was dissolved in 1 mL of methanol, and subjected to GC-MS and LC-MS/MS. Hair samples were washed and cut into approximately 2 mm sections, then ground to powder by a low-temperature grinder. Twenty mg of the hair powder was extracted with 1 mL of methanol, and the supernatant was subjected to LC-MS/MS.</p><p><strong>Results: </strong>Etomidate, metomidate, propoxate, and isopropoxate were chromatographically separated and each mass spectrum was obtained by GC-MS. For LC-MS/MS, tested validation data were all satisfactory. The seized powder samples contained isopropoxate, with an approximate content of 30.9%. Etomidate, etomidate acid, metomidate, and isopropoxate could be determined in the submitted hairs, ranging from 2.89 to 8.09 ng/mg, 0.0591-0.177 ng/mg, 0.342-2.77 ng/mg, and 33.2-130 ng/mg, respectively.</p><p><strong>Conclusions: </strong>Mass spectra and ion chromatograms of etomidate, metomidate, isopropoxate, and propoxate were obtained by GC-MS. We have also established a simultaneous and reliable analytical method for etomidate, etomidate acid, metomidate, and isopropoxate in human hair by LC-MS/MS. This is the first report to present analytical results of a novel imidazole-derived GABA agonist isopropoxate in drug abuse cases.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"190-205"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817361","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}