Forensic Toxicology最新文献

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Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway. 水飞蓟素通过 Keap1-Nrf2/heme oxygenase-1 信号通路改善重氮农诱导的大鼠亚急性肾毒性
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2025-01-01 Epub Date: 2024-08-08 DOI: 10.1007/s11419-024-00697-x
Eman Mohamed Fath, Hatem H Bakery, Ragab M El-Shawarby, Mohamed E S Abosalem, Samar S Ibrahim, Nesrine Ebrahim, Ahmed Medhat Hegazy
{"title":"Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.","authors":"Eman Mohamed Fath, Hatem H Bakery, Ragab M El-Shawarby, Mohamed E S Abosalem, Samar S Ibrahim, Nesrine Ebrahim, Ahmed Medhat Hegazy","doi":"10.1007/s11419-024-00697-x","DOIUrl":"10.1007/s11419-024-00697-x","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of the current study was to clarify the potential molecular mechanism underlying the protective effects of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of the Kelch-like-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in minimizing the oxidative stress induced by diazinon (DZN).</p><p><strong>Methods: </strong>Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4 weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests. Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and histopathological examination.</p><p><strong>Results: </strong>SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of HO-1, a crucial target enzyme of Nrf2.</p><p><strong>Conclusions: </strong>SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"62-73"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906326","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
Benzoylmesaconine alters the native structure and activity of hen egg white lysozyme: revealing possible mechanism of aconitum-induced toxicity. 苯甲酰美乌碱改变蛋清溶菌酶的天然结构和活性:揭示乌头中毒的可能机制。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-12-21 DOI: 10.1007/s11419-024-00709-w
Manka Marycleopha, Jennifer Johnson, Abhishek Singh, Satish Kumar
{"title":"Benzoylmesaconine alters the native structure and activity of hen egg white lysozyme: revealing possible mechanism of aconitum-induced toxicity.","authors":"Manka Marycleopha, Jennifer Johnson, Abhishek Singh, Satish Kumar","doi":"10.1007/s11419-024-00709-w","DOIUrl":"https://doi.org/10.1007/s11419-024-00709-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study examines the interaction between benzoylmesaconine (BMA) and hen egg white lysozyme (HEWL) under various physiological conditions, aiming to determine how BMA affects the HEWL's structure and function.</p><p><strong>Methods: </strong>Several analytical techniques were used, including tryptophan assay, light scattering, thioflavin T (ThT)-binding assay, dynamic light scattering, 8-anilino-1-naphthalenesulfonic acid (ANS)-binding assay, circular dichroism (CD) spectroscopy, enzyme activity assay, and molecular docking.</p><p><strong>Results: </strong>The tryptophan assay displayed a concentration-dependent decrease in tryptophan fluorescence, showing an interaction between BMA and HEWL. Light scattering and ThT-binding assays confirmed increased protein aggregation and amyloid fibril formation, while the ANS-binding assay demonstrated altered exposed hydrophobic regions, implying structural changes. CD spectroscopy showed a reduction in α-helix content, indicating conformational alterations, and enzyme activity assays showed a loss of lytic function due to structural distortion. Finally, molecular docking identified significant bonds and hydrophobic interactions between BMA and HEWL residues.</p><p><strong>Conclusions: </strong>BMA binding induces structural changes in proteins, forming small oligomers and amyloid fibrils that decrease HEWL enzymatic activity and disrupt functional integrity.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871909","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
Method for determination of cytisine in post-mortem biological matrices and its application to two forensic cases. 死后生物基质中胱氨酸的测定方法及其在两个法医案例中的应用。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-12-19 DOI: 10.1007/s11419-024-00710-3
Karolina Nowak, Paweł Szpot, Marcin Zawadzki, Agnieszka Chłopaś-Konowałek
{"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":"https://doi.org/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-d<sub>4</sub> 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":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","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}
引用次数: 0
Urinary excretion profiles of the orexin receptor antagonist suvorexant and its metabolites. 食欲素受体拮抗剂suvoexant及其代谢产物的尿排泄谱。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-12-18 DOI: 10.1007/s11419-024-00706-z
Misato Wada, Hiroe Kamata, Noriaki Shima, Atsushi Nitta, Hidenao Kakehashi, Shihoko Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Hiroshi Nishioka
{"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-18","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}
引用次数: 0
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. 一种新型咪唑衍生GABA激动剂异丙酸酯的鉴定:用LC-MS/MS同时检测和定量滥用病例中人类头发中咪唑衍生类似物
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-12-12 DOI: 10.1007/s11419-024-00707-y
Xiaolong Zhang, Yuxuan Chen, Jinlei Liu, Mengchao Wang, Yinyin Dai, Kundi Zhao, Jie Gu, Huimin Zhang, Amin Wurita, Koutaro Hasegawa
{"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","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}
引用次数: 0
Elucidation of toxic effects of 1,2-diacetylbenzene: an in silico study 阐明 1,2-二乙酰基苯的毒性效应:硅学研究
IF 2.2 4区 医学
Forensic Toxicology Pub Date : 2024-09-19 DOI: 10.1007/s11419-024-00702-3
Hai Duc Nguyen, Giang Huong Vu, Linh Thuy Hoang, Min-Sun Kim
{"title":"Elucidation of toxic effects of 1,2-diacetylbenzene: an in silico study","authors":"Hai Duc Nguyen, Giang Huong Vu, Linh Thuy Hoang, Min-Sun Kim","doi":"10.1007/s11419-024-00702-3","DOIUrl":"https://doi.org/10.1007/s11419-024-00702-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>We aimed to explore the metabolite products of 1,2-diacetylbenzene (DAB) and investigate their harmful effects, physicochemical properties, and biological activities, along with those of DAB itself.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Key approaches included MetaTox, PASS online, ADMESWISS, ADMETlab 2.0, molecular docking, and molecular dynamic simulation to identify metabolites, toxic effects, Lipinski’s rule criteria, absorption, distribution, metabolism, and excretion properties, interactions with cytochrome (CYP) 450 isoforms, and the stability of the DAB-cytochrome complex.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 13 metabolite products from DAB were identified, involving Phase I reactions (aliphatic hydroxylation, epoxidation, oxidative dehydrogenation, and hydrogenation) and Phase II reactions (oxidative sulfation and methylation). Molecular dynamics and modeling revealed a stable interaction between CYP1A2 and DAB, suggesting the involvement of CYP1A2 in DAB metabolism. All studied compounds adhered to Lipinski’s rule, indicating their potential as inducers or activators of toxic mechanisms. The physicochemical parameters and pharmacokinetics of the investigated compounds were consistent with their harmful effects, which included neurotoxic, nephrotoxic, endocrine disruptor, and hepatotoxic consequences due to their high gastrointestinal absorption and ability to cross the blood–brain barrier. Various CYP450 isoforms exhibited different functions, and the compounds were found to act as superoxide dismutase inhibitors, neuropeptide Y2 antagonists, glutaminase inhibitors, and activators of caspases 3 and 8. DAB and its metabolites were also associated with apoptosis, oxidative stress, and neuroendocrine disruption.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The toxic effects of DAB and its metabolites were predicted in this study. Further research is warranted to explore their effects on other organs, such as the liver and kidneys, and to validate our findings.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252049","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
Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse 生物信息学驱动的非靶向代谢组学分析用于甲基苯丙胺滥用的临床筛查
IF 2.2 4区 医学
Forensic Toxicology Pub Date : 2024-09-18 DOI: 10.1007/s11419-024-00703-2
Elif Kesmen, Hızır Asliyüksek, Ahmet Nezih Kök, Cem Şenol, Semih Özli, Onur Senol
{"title":"Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse","authors":"Elif Kesmen, Hızır Asliyüksek, Ahmet Nezih Kök, Cem Şenol, Semih Özli, Onur Senol","doi":"10.1007/s11419-024-00703-2","DOIUrl":"https://doi.org/10.1007/s11419-024-00703-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid–liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Significantly, altered metabolites were identified by the fold analysis and Welch’s test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"39 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252052","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
Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC–MS/MS using standard addition method 采用标准添加法,通过气相色谱-质谱/质谱分析罗哌卡因及其代谢物在人体液和固体组织中的尸后分布情况
IF 2.2 4区 医学
Forensic Toxicology Pub Date : 2024-09-16 DOI: 10.1007/s11419-024-00695-z
Xiaolong Zhang, Shuyun Wang, Yuxuan Chen, Jie Gu, Mengchao Wang, Yinyin Dai, Kundi Zhao, Yue Wang, Amin Wurita, Koutaro Hasegawa
{"title":"Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC–MS/MS using standard addition method","authors":"Xiaolong Zhang, Shuyun Wang, Yuxuan Chen, Jie Gu, Mengchao Wang, Yinyin Dai, Kundi Zhao, Yue Wang, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-024-00695-z","DOIUrl":"https://doi.org/10.1007/s11419-024-00695-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>An analytical method was developed for determining ropivacaine and its main metabolite, 3-hydroxyropivacaine in biomedical samples using gas chromatography-tandem mass spectrometry (GC–MS/MS). Then, this established method was applied to investigate the distribution of ropivacaine and its metabolite in human fluids and solid tissues obtained from an authentic case ropivacaine involved.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The fluid sample was added acetonitrile, and solid tissue was homogenized using a freezer mill and then added into acetonitrile. Then, an internal standard solution was added to the mixtures. The mixture was centrifuged at 12,000 × g for 5 min, and the upper layer of acetonitrile was transferred to magnesium sulfate and octadecyl silica (C18) gel for cleaning up the sample. After centrifugation, the upper layer was then evaporated to dryness with nitrogen, and dissolved with methanol, then injected into the GC–MS/MS system.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The coefficients of determination (r<sup>2</sup>) of constructed calibration curves were all greater than 0.999. The limits of detection for ropivacaine and 3-hydroxyropivacaine in target samples were 15 ng/mL and 10 ng/mL, respectively. The recovery rates of ropivacaine and 3-hydroxyropivacaine ranged from 97.6% to 103% and from 96.5% to 104%, respectively. The inter-day precision values of ropivacaine and 3-hydroxyropivacaine were not greater than 6.25% and 7.98%, respectively, and the inter-day trueness values were not greater than 6.90% and 8.33%, respectively; the intra-day precision and trueness values of ropivacaine and 3-hydroxyropivacaine were not greater than 3.20%, 6.78%, 7.84% and 8.99%, respectively.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>GC–MS/MS method for simultaneous detection and quantification of ropivacaine and 3-hydroxyropivacaine in biological samples was successfully developed. The method could also be applied to samples obtained from an authentic case; their distribution among tested fluids and solid tissues were also measured. This is the first report on the distribution of ropivacaine and its major metabolite 3-hydroxyropivacaine in a human case.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"21 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269773","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
Development of an LC-MS/MS method for the determination of five psychoactive drugs in postmortem urine by optimization of enzymatic hydrolysis of glucuronide conjugates. 通过优化葡萄糖醛酸苷共轭物的酶水解,建立测定死后尿液中五种精神活性药物的 LC-MS/MS 方法。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-07-01 Epub Date: 2024-04-01 DOI: 10.1007/s11419-024-00685-1
Tomohito Matsuo, Tadashi Ogawa, Masae Iwai, Katsutoshi Kubo, Fumio Kondo, Hiroshi Seno
{"title":"Development of an LC-MS/MS method for the determination of five psychoactive drugs in postmortem urine by optimization of enzymatic hydrolysis of glucuronide conjugates.","authors":"Tomohito Matsuo, Tadashi Ogawa, Masae Iwai, Katsutoshi Kubo, Fumio Kondo, Hiroshi Seno","doi":"10.1007/s11419-024-00685-1","DOIUrl":"10.1007/s11419-024-00685-1","url":null,"abstract":"<p><strong>Purpose: </strong>Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ<sup>9</sup>-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline).</p><p><strong>Methods: </strong>The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation.</p><p><strong>Results: </strong>We found that the recombinant β-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r<sup>2</sup> values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%.</p><p><strong>Conclusions: </strong>We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"181-190"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335341","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
Intracerebral hemorrhage in methanol toxicity patients during COVID-19 pandemic: case report and review of literature. COVID-19 大流行期间甲醇中毒患者的脑内出血:病例报告和文献综述。
IF 2.8 4区 医学
Forensic Toxicology Pub Date : 2024-07-01 Epub Date: 2024-02-09 DOI: 10.1007/s11419-023-00680-y
Hosein Safari, Reza Ajudani, Mohsen Savaie, Armin Jahangiri Babadi, Pooyan Alizadeh
{"title":"Intracerebral hemorrhage in methanol toxicity patients during COVID-19 pandemic: case report and review of literature.","authors":"Hosein Safari, Reza Ajudani, Mohsen Savaie, Armin Jahangiri Babadi, Pooyan Alizadeh","doi":"10.1007/s11419-023-00680-y","DOIUrl":"10.1007/s11419-023-00680-y","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to examine the clinical and imaging manifestations of methanol toxicity during the COVID-19 pandemic, as well as to review existing studies on this topic. The most common cause of methanol intoxication is methanol-adulterated liquor. The primary metabolite of methanol, formic acid, is responsible for pathological changes. Symptoms typically present within 6-24 h of consumption and can include visual disturbances, acute neurological symptoms, and gastrointestinal issues. During the initial year of the COVID-19 pandemic, methanol poisoning cases increased significantly.</p><p><strong>Methods: </strong>In this study, We present six different patients with methanol intoxication and their clinical and imaging features.</p><p><strong>Results: </strong>In the literature review, the most common clinical presentation was loss of consciousness and obtundation and the other was vision loss. CT scan findings showed bilateral putaminal necrosis and hemorrhage in 55% of methanol toxicity patients.</p><p><strong>Conclusion: </strong>Methanol intoxication, causing bilateral putaminal involvement and a 50% mortality rate in intracerebral hemorrhage patients, warrants urgent toxicological analysis due to potential putaminal hemorrhage.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"242-247"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706501","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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