首页 > 最新文献

Forensic Toxicology最新文献

英文 中文
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 Q2 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

Purpose

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.

Methods

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.

Results

The coefficients of determination (r2) 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.

Conclusions

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.

目的 建立了一种气相色谱-串联质谱(GC-MS/MS)测定生物医学样品中罗哌卡因及其主要代谢物3-羟基丙哌卡因的分析方法。方法 液体样品加入乙腈,固体组织用冷冻粉碎机匀浆后加入乙腈。然后在混合物中加入内标溶液。将混合物在 12,000 × g 转速下离心 5 分钟,然后将上层乙腈转移到硫酸镁和十八烷基硅胶(C18)凝胶上进行样品净化。结果 构建的校正曲线的测定系数(r2)均大于 0.999。目标样品中罗哌卡因和 3-hydroxyropivacaine 的检出限分别为 15 ng/mL 和 10 ng/mL。罗哌卡因和 3-羟基丙哌卡因的回收率分别为 97.6% 至 103% 和 96.5% 至 104%。罗哌卡因和 3-羟基丙哌卡因的日间精密度值分别不大于 6.25% 和 7.98%,日间真实度值分别不大于 6.90% 和 8.33%;罗哌卡因和 3-羟基丙哌卡因的日内精密度值和真实度值分别不大于 3.结论 成功建立了同时检测和定量生物样品中罗哌卡因和3-羟基丙哌卡因的GC-MS/MS方法。该方法还可应用于从真实病例中获得的样本,并测定了它们在被测体液和固体组织中的分布。这是首次报道罗哌卡因及其主要代谢物 3-羟基丙哌卡因在人体病例中的分布情况。
{"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 Q2 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

Purpose: 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-Δ9-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline).

Methods: 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.

Results: 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 r2 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%.

Conclusions: 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.

目的:生物样本的毒理学分析在法医和临床调查中发挥着重要作用。摄入的药物会以与葡萄糖醛酸等内源性物质共轭的形式排泄到尿液中;水解这些共轭物可提高液相色谱-串联质谱法(LC-MS/MS)对目标药物的测定。在本研究中,我们试图改进五种精神活性药物(11-去甲-9-羧基-Δ9-四氢大麻酚、奥沙西泮、劳拉西泮、替马西泮和阿米替林)葡萄糖醛酸轭合物的酶水解:通过改变温度、酶量和反应时间来优化尿液中葡萄糖醛酸共轭物的酶水解效率。水解直接在提取柱上进行。经过充分验证后,将这种使用 LC-MS/MS 的分析方法应用于法医尸检样本:结果:我们发现,重组β-葡糖醛酸酶 B-One® 可在室温下直接在提取柱上 3 分钟内定量水解这些共轭物。这种柱上方法节省了时间,并避免了宝贵样品在转移到提取柱过程中的损失。用这种方法处理的基于 LC-MS/MS 的校准曲线显示出良好的线性关系,r2 值超过 0.998。该方法的日内和日间准确度和精密度分别为 93.0-109.7% 和 0.8-8.8%。回收率为 56.1-104.5%。基质效应为 78.9% 至 126.9%:我们建立了一种直接在萃取柱上酶水解尿液中葡萄糖醛酸苷结合物的 LC-MS/MS 方法。该方法已成功应用于法医尸检样本。该方法应用广泛,包括法医和临床毒理学研究。
{"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 Q2 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

Purpose: 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.

Methods: In this study, We present six different patients with methanol intoxication and their clinical and imaging features.

Results: 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.

Conclusion: Methanol intoxication, causing bilateral putaminal involvement and a 50% mortality rate in intracerebral hemorrhage patients, warrants urgent toxicological analysis due to potential putaminal hemorrhage.

目的:本研究旨在探讨 COVID-19 大流行期间甲醇中毒的临床和影像学表现,并回顾现有的相关研究。甲醇中毒最常见的原因是掺有甲醇的白酒。甲醇的主要代谢产物甲酸会导致病理变化。症状通常在饮用后 6-24 小时内出现,包括视觉障碍、急性神经症状和胃肠道问题。在 COVID-19 大流行的最初一年,甲醇中毒病例显著增加:在本研究中,我们介绍了六名不同的甲醇中毒患者及其临床和影像学特征:在文献综述中,最常见的临床表现是意识丧失和昏迷,另一种是视力丧失。CT扫描结果显示,55%的甲醇中毒患者出现双侧副乳头坏死和出血:结论:甲醇中毒会导致双侧副中枢受累,脑出血患者的死亡率为 50%,因此需要对潜在的副中枢出血进行紧急毒理学分析。
{"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
The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid. 合成大麻素 NPB-22 的生物效应和热降解。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-31 DOI: 10.1007/s11419-023-00679-5
Akihiro Takeda, Takahiro Doi, Akiko Asada, Katsuhiro Yuzawa, Akemichi Nagasawa, Kai Igarashi, Tomokazu Maeno, Atsuko Suzuki, Seiko Shimizu, Nozomi Uemura, Jun'ichi Nakajima, Toshinari Suzuki, Akiko Inomata, Takaomi Tagami

Purpose: NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.

Methods: The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB1 and CB2 were investigated using [35S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector.

Results: NPB-22 and Adamantyl-THPINACA had equivalent CB1 activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB1 activity.

Conclusion: It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB1 activity in vitro.

目的:对 NPB-22(1-戊基-1H-吲唑-3-羧酸喹啉-8-基酯)、Adamantyl-THPINACA(N-(1-金刚烷基)-1-[(四氢-2H-吡喃-4-基)甲基]-1H-吲唑-3-甲酰胺)和 CUMYL-4CN-B7AICA (1-(4-氰基丁基)-N-(2-苯基丙-2-基)-1H-吡咯并[2、3-b]吡啶-3-甲酰胺)合成大麻素的 CB1(大麻素受体 1 型)和 CB2(大麻素受体 2 型)活性进行了评估,并研究了它们吸入类似香烟的生物效应。方法:使用[35S]鸟苷-5'-O-(3-硫代)-三磷酸结合试验研究了上述合成大麻素在 CB1 和 CB2 上的半数最大有效浓度值。此外,还利用小鼠吸入暴露试验评估了它们的生物效应。在侏儒撞击器中用有机溶剂回收了产生的烟雾,并使用液相色谱-光电二极管阵列检测器对烟雾成分的热降解化合物进行了鉴定和定量:结果:NPB-22 和 Adamantyl-THPINACA 在体外实验中具有同等的 CB1 活性。同时,在吸入暴露试验中,NPB-22 对某些项目的生物效应弱于 Adamantyl-THPINACA。在分析侏儒撞击器中的有机溶剂时发现,NPB-22 通过燃烧降解为 8-喹啉醇和戊基吲唑-3-羧酸。此外,这些降解化合物没有 CB1 活性:结论:据估计,NPB-22 在吸入暴露试验中的生物效应有所减弱,这是因为它在燃烧过程中发生了热降解,而由此产生的降解化合物在体外没有任何 CB1 活性。
{"title":"The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid.","authors":"Akihiro Takeda, Takahiro Doi, Akiko Asada, Katsuhiro Yuzawa, Akemichi Nagasawa, Kai Igarashi, Tomokazu Maeno, Atsuko Suzuki, Seiko Shimizu, Nozomi Uemura, Jun'ichi Nakajima, Toshinari Suzuki, Akiko Inomata, Takaomi Tagami","doi":"10.1007/s11419-023-00679-5","DOIUrl":"10.1007/s11419-023-00679-5","url":null,"abstract":"<p><strong>Purpose: </strong>NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB<sub>1</sub> (cannabinoid receptor type 1) and CB<sub>2</sub> (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.</p><p><strong>Methods: </strong>The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB<sub>1</sub> and CB<sub>2</sub> were investigated using [<sup>35</sup>S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector.</p><p><strong>Results: </strong>NPB-22 and Adamantyl-THPINACA had equivalent CB<sub>1</sub> activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB<sub>1</sub> activity.</p><p><strong>Conclusion: </strong>It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB<sub>1</sub> activity in vitro.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"142-151"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641985","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
Rapid screening of riot control agents using DART-TD-HRMS. 利用 DART-TD-HRMS 快速筛选防暴制剂。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-02-22 DOI: 10.1007/s11419-024-00681-5
Lina Mörén, Anders Östin, Andreas Larsson, Julia Forsberg, Daniel Wiktelius, Pernilla Lindén

Purpose: Riot Control Agents (RCAs) are chemicals used in law enforcement for non-lethal riot control and use in conflicts between states that violates the Chemical Weapons Convention. OPCW's Scientific Advisory Board has identified sixteen potential RCAs including capsaicinoids, CS, and CR. RCAs may be misused for criminal purposes, so methods for detecting such misuse are needed. This study therefore evaluates the feasibility of a rapid, high throughput screening method of RCAs on surfaces (particularly clothing surfaces) by Direct Analysis in Real Time with a thermal desorption unit coupled to high-resolution mass spectrometry (DART-TD-HRMS).

Methods: A broadly applicable method for detecting potential RCAs was developed and tested on cotton fabric samples sprayed with self-defence sprays from an in-house reference stock. The feasibility of detecting RCAs by direct analysis of surface wipe samples placed in the DART source was also investigated.

Results: The method detected all sixteen RCAs and contaminated clothing were successfully screened for active agents in a reference collection of self-defence sprays. A pilot study also showed that RCAs can be detected by holding a sample directly in front of the DART source.

Conclusion: DART-TD-HRMS enables rapid and simple screening of RCAs on fabric samples enabling a high sample throughput.

目的:骚乱控制剂(RCAs)是执法部门用于非致命性骚乱控制的化学品,也可用于违反《化学武器公约》的国家间冲突。禁止化学武器组织的科学顾问委员会已经确定了十六种潜在的 RCA,包括辣椒素、CS 和 CR。RCA 可能会被滥用于犯罪目的,因此需要找到检测此类滥用的方法。因此,本研究评估了通过热脱附装置与高分辨率质谱联用直接实时分析法(DART-TD-HRMS)对表面(尤其是衣物表面)上的 RCA 进行快速、高通量筛选的可行性:方法:开发了一种广泛适用的检测潜在 RCA 的方法,并在喷洒了自卫喷雾剂的棉织物样品上进行了测试。此外,还研究了通过直接分析置于 DART 源中的表面擦拭样本来检测 RCA 的可行性:结果:该方法检测出了所有 16 种 RCA,并成功地在自卫喷雾剂参考样品集中对受污染的衣物进行了活性剂筛查。一项试验研究还表明,将样品直接放在 DART 源前也能检测出 RCA:结论:DART-TD-HRMS 可以对织物样品上的 RCA 进行快速、简单的筛查,从而提高样品处理量。
{"title":"Rapid screening of riot control agents using DART-TD-HRMS.","authors":"Lina Mörén, Anders Östin, Andreas Larsson, Julia Forsberg, Daniel Wiktelius, Pernilla Lindén","doi":"10.1007/s11419-024-00681-5","DOIUrl":"10.1007/s11419-024-00681-5","url":null,"abstract":"<p><strong>Purpose: </strong>Riot Control Agents (RCAs) are chemicals used in law enforcement for non-lethal riot control and use in conflicts between states that violates the Chemical Weapons Convention. OPCW's Scientific Advisory Board has identified sixteen potential RCAs including capsaicinoids, CS, and CR. RCAs may be misused for criminal purposes, so methods for detecting such misuse are needed. This study therefore evaluates the feasibility of a rapid, high throughput screening method of RCAs on surfaces (particularly clothing surfaces) by Direct Analysis in Real Time with a thermal desorption unit coupled to high-resolution mass spectrometry (DART-TD-HRMS).</p><p><strong>Methods: </strong>A broadly applicable method for detecting potential RCAs was developed and tested on cotton fabric samples sprayed with self-defence sprays from an in-house reference stock. The feasibility of detecting RCAs by direct analysis of surface wipe samples placed in the DART source was also investigated.</p><p><strong>Results: </strong>The method detected all sixteen RCAs and contaminated clothing were successfully screened for active agents in a reference collection of self-defence sprays. A pilot study also showed that RCAs can be detected by holding a sample directly in front of the DART source.</p><p><strong>Conclusion: </strong>DART-TD-HRMS enables rapid and simple screening of RCAs on fabric samples enabling a high sample throughput.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"152-162"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930670","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
Development of a simple screening method for analyzing cereulide toxin in fried rice using liquid chromatography-tandem mass spectrometry. 利用液相色谱-串联质谱法开发分析炒米中麦角内酯毒素的简易筛选方法。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-22 DOI: 10.1007/s11419-024-00683-3
Hiroshi Koike, Maki Kanda, Chie Monma, Souichi Yoshikawa, Hiroshi Hayashi, Yoko Matsushima, Yumi Ohba, Momoka Hayashi, Natsumi Furuta, Wakaba Okada, Chieko Nagano, Keiko Yokoyama, Tomoko Yokoyama, Takeo Sasamoto

Purpose: The presence of cereulide, an emetic toxin produced by Bacillus cereus, in fried rice samples is critical evidence of food poisoning even in situations where B. cereus could not be detected. This study aims to develop a screening method for analyzing cereulide in fried rice using the QuEChERS procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Methods: Cereulide was identified and quantified in fried rice samples using the QuEChERS extraction method and LC-MS/MS. The accuracies of the methods were determined by analyzing fortified blank samples at two concentrations (10 and 50 µg/kg) conducted on three samples daily for five days.

Results: The QuEChERS procedure removed matrix compounds from fried rice. Characteristic MS/MS spectra enabled the identification of cereulide. As the matrix effects in seven fried rice samples were within ± 6%, an external solvent calibration curve could be used for quantification. This method exhibited good accuracy ranging from 88 to 89%. The relative standard deviations for both repeatability and intra-laboratory reproducibility were < 4%. These standard deviations satisfied the criteria of the Japanese validation guidelines for residues (MHLW 2010, Director Notice, Syoku-An No. 1224-1). The limit of quantification was 2 μg/kg. The applicability of this method was confirmed using the analysis of cereulide in fried rice samples incubated with emetic Bacillus cereus.

Conclusions: The QuEChERS extraction procedure described herein showed substantial promise as a reliable screening tool for cereulide in fried rice sample.

目的:即使在无法检测到蜡样芽孢杆菌的情况下,炒饭样本中存在蜡样芽孢杆菌内酯(一种由蜡样芽孢杆菌产生的催吐毒素)也是食物中毒的重要证据。本研究旨在利用 QuEChERS 程序和液相色谱-串联质谱法(LC-MS/MS),开发一种分析炒饭中蜡样内酯的筛选方法:方法:采用 QuEChERS 萃取法和液相色谱-串联质谱法对炒米样品中的谷维素进行鉴定和定量。结果:QuEChERS 方法去除了样品中的基质(10 微克/千克和 50 微克/千克),而 LC-MS/MS 方法去除了样品中的基质(10 微克/千克和 50 微克/千克),而 LC-MS/MS 方法去除了样品中的基质(50 微克/千克):结果:QuEChERS 程序可去除炒米中的基质化合物。通过特征性的 MS/MS 图谱可以鉴定出麦角苷。由于 7 个炒米样品中的基质效应在 ± 6% 以内,因此可以使用外部溶剂校准曲线进行定量。该方法的准确度为88%至89%。重复性和实验室内重现性的相对标准偏差均为结论:本文所述的 QuEChERS 提取程序作为一种可靠的筛查炒米样品中谷胱甘肽的工具,显示出了巨大的潜力。
{"title":"Development of a simple screening method for analyzing cereulide toxin in fried rice using liquid chromatography-tandem mass spectrometry.","authors":"Hiroshi Koike, Maki Kanda, Chie Monma, Souichi Yoshikawa, Hiroshi Hayashi, Yoko Matsushima, Yumi Ohba, Momoka Hayashi, Natsumi Furuta, Wakaba Okada, Chieko Nagano, Keiko Yokoyama, Tomoko Yokoyama, Takeo Sasamoto","doi":"10.1007/s11419-024-00683-3","DOIUrl":"10.1007/s11419-024-00683-3","url":null,"abstract":"<p><strong>Purpose: </strong>The presence of cereulide, an emetic toxin produced by Bacillus cereus, in fried rice samples is critical evidence of food poisoning even in situations where B. cereus could not be detected. This study aims to develop a screening method for analyzing cereulide in fried rice using the QuEChERS procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Methods: </strong>Cereulide was identified and quantified in fried rice samples using the QuEChERS extraction method and LC-MS/MS. The accuracies of the methods were determined by analyzing fortified blank samples at two concentrations (10 and 50 µg/kg) conducted on three samples daily for five days.</p><p><strong>Results: </strong>The QuEChERS procedure removed matrix compounds from fried rice. Characteristic MS/MS spectra enabled the identification of cereulide. As the matrix effects in seven fried rice samples were within ± 6%, an external solvent calibration curve could be used for quantification. This method exhibited good accuracy ranging from 88 to 89%. The relative standard deviations for both repeatability and intra-laboratory reproducibility were < 4%. These standard deviations satisfied the criteria of the Japanese validation guidelines for residues (MHLW 2010, Director Notice, Syoku-An No. 1224-1). The limit of quantification was 2 μg/kg. The applicability of this method was confirmed using the analysis of cereulide in fried rice samples incubated with emetic Bacillus cereus.</p><p><strong>Conclusions: </strong>The QuEChERS extraction procedure described herein showed substantial promise as a reliable screening tool for cereulide in fried rice sample.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"163-171"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193555","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
Short- and long-term stability of synthetic cathinones and dihydro-metabolites in human urine samples. 合成卡西酮和二氢代谢物在人体尿样中的短期和长期稳定性。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-30 DOI: 10.1007/s11419-024-00684-2
Abdulaziz A Aldubayyan, Erika Castrignanò, Simon Elliott, Vincenzo Abbate

Purpose: Synthetic cathinones constitute the second largest group of new psychoactive substances, which are often used for recreational purposes and reported in toxicological analysis. Various factors may influence the stability of synthetic cathinones between sampling and analysis, and therefore, stability studies are required to determine the best storage conditions as well as extend the period of detection.

Methods: This study involved sixteen synthetic cathinones and ten dihydro-metabolites spiked in human urine to evaluate the stability under common storage conditions to imitate real forensic toxicology samples. The samples were stored at either room temperature (22-23 °C) for up to 3 days, refrigerated (4 °C) for up to 14 days or frozen (-40 °C) for up to 12 months, and analyzed in triplicate using a validated liquid chromatography-tandem mass spectrometry method.

Results: Analytes' concentrations decreased over time, although slower when stored frozen. All analytes remained stable (> 80%) for 1 month when stored frozen before losses in content were more apparent for some compounds, depending on their chemical structure. Under all storage conditions, the highest instability was observed for analytes containing halogens (i.e., chlorine or fluorine). Thus, halogenated analytes were further investigated by using liquid chromatography coupled to quadruple time-of-flight mass spectrometry to attempt identifying degradation products.

Conclusions: Irrespective of parent analytes, dihydro-metabolites had improved stability at each tested temperature, which highlights their importance as appropriate urine biomarkers when retesting is required after a long period of storage.

目的:合成卡西酮是第二大类新型精神活性物质,经常被用于娱乐目的,并在毒理学分析中被报告。从采样到分析期间,各种因素都可能影响合成卡西酮的稳定性,因此需要进行稳定性研究,以确定最佳储存条件并延长检测期:本研究在人体尿液中添加了十六种合成卡西酮和十种二氢代谢物,以评估它们在普通储存条件下的稳定性,从而模仿真实的法医毒理学样本。样品在室温(22-23 °C)下最多储存 3 天,在冷藏(4 °C)下最多储存 14 天,或在冷冻(-40 °C)下最多储存 12 个月,并采用经过验证的液相色谱-串联质谱法对一式三份样品进行分析:结果:分析物的浓度随着时间的推移而下降,但冷冻保存时下降较慢。所有分析物在冷冻保存 1 个月后仍保持稳定(> 80%),某些化合物的含量损失更为明显,这取决于其化学结构。在所有储存条件下,含有卤素(即氯或氟)的分析物的不稳定性最高。因此,我们使用液相色谱法和四重飞行时间质谱法对卤代分析物进行了进一步研究,试图找出降解产物:无论母体分析物如何,二氢代谢物在每个测试温度下的稳定性都有所提高,这突出了它们在长期储存后需要重新测试时作为合适的尿液生物标记物的重要性。
{"title":"Short- and long-term stability of synthetic cathinones and dihydro-metabolites in human urine samples.","authors":"Abdulaziz A Aldubayyan, Erika Castrignanò, Simon Elliott, Vincenzo Abbate","doi":"10.1007/s11419-024-00684-2","DOIUrl":"10.1007/s11419-024-00684-2","url":null,"abstract":"<p><strong>Purpose: </strong>Synthetic cathinones constitute the second largest group of new psychoactive substances, which are often used for recreational purposes and reported in toxicological analysis. Various factors may influence the stability of synthetic cathinones between sampling and analysis, and therefore, stability studies are required to determine the best storage conditions as well as extend the period of detection.</p><p><strong>Methods: </strong>This study involved sixteen synthetic cathinones and ten dihydro-metabolites spiked in human urine to evaluate the stability under common storage conditions to imitate real forensic toxicology samples. The samples were stored at either room temperature (22-23 °C) for up to 3 days, refrigerated (4 °C) for up to 14 days or frozen (-40 °C) for up to 12 months, and analyzed in triplicate using a validated liquid chromatography-tandem mass spectrometry method.</p><p><strong>Results: </strong>Analytes' concentrations decreased over time, although slower when stored frozen. All analytes remained stable (> 80%) for 1 month when stored frozen before losses in content were more apparent for some compounds, depending on their chemical structure. Under all storage conditions, the highest instability was observed for analytes containing halogens (i.e., chlorine or fluorine). Thus, halogenated analytes were further investigated by using liquid chromatography coupled to quadruple time-of-flight mass spectrometry to attempt identifying degradation products.</p><p><strong>Conclusions: </strong>Irrespective of parent analytes, dihydro-metabolites had improved stability at each tested temperature, which highlights their importance as appropriate urine biomarkers when retesting is required after a long period of storage.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"172-180"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329766","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
Can the cyanide metabolite, 2-aminothiazoline-4-carboxylic acid, be used for forensic verification of cyanide poisoning? 氰化物代谢物 2-氨基噻唑啉-4-羧酸能否用于氰化物中毒的法医鉴定?
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-13 DOI: 10.1007/s11419-024-00690-4
Abdullah H Alluhayb, Carter Severance, Tara Hendry-Hofer, Vikhyat S Bebarta, Brian A Logue

Purpose: Forensic verification of cyanide (CN) poisoning by direct CN analysis in postmortem blood is challenging due to instability of CN in biological samples. CN metabolites, thiocyanate (SCN-) and 2-aminothiazoline-4-carboxylic acid (ATCA), have been proposed as more stable biomarkers, yet it is unclear if either is appropriate for this purpose. In this study, we evaluated the behavior of CN biomarkers in postmortem swine and postmortem blood to determine which serves as the best biomarker of CN exposure.

Methods: CN, SCN-, and ATCA were measured in postmortem swine (N = 8) stored at 4 °C and postmortem blood stored at 25 °C (room temperature, RT) and 37 °C (typical human body temperature, HBT).

Results: Following CN poisoning, the concentration of each CN biomarker increased well above the baseline. In postmortem swine, CN concentrations declined rapidly (t1/2 = 34.3 h) versus SCN- (t1/2 = 359 h, 15 days) and ATCA (t1/2 = 544 h, 23 days). CN instability in postmortem blood increased at RT (t1/2 = 10.7 h) and HBT (t1/2 = 6.6 h). SCN- and ATCA were more stable than CN at all storage conditions. In postmortem swine, the t1/2s of SCN- and ATCA were 15 and 23 days, respectively. While both the t1/2s of SCN- and ATCA were relatively lengthy, endogenous levels of SCN- were much more variable than ATCA.

Conclusion: While there are still questions to be answered, ATCA was the most adept forensic marker of CN poisoning (i.e., ATCA produced the longest half-life, the largest increase above baseline levels, and most stable background concentrations).

目的:由于氰化物在生物样本中的不稳定性,通过对尸体血液中的氰化物进行直接分析来对氰化物(CN)中毒进行法医验证具有挑战性。有人建议将氯化萘代谢物硫氰酸盐(SCN-)和 2-氨基噻唑啉-4-羧酸(ATCA)作为更稳定的生物标记物,但目前尚不清楚这两种生物标记物是否适用于这一目的。在本研究中,我们评估了猪死后和死后血液中氯化萘生物标记物的行为,以确定哪种生物标记物最适合作为氯化萘暴露的生物标记物:方法:在4 °C保存的猪尸体(N = 8)和25 °C(室温,RT)和37 °C(典型人体温度,HBT)保存的尸体血液中测量氯化萘、SCN-和ATCA:结果:氯化萘中毒后,每种氯化萘生物标志物的浓度都远高于基线。与 SCN-(t1/2 = 359 小时,15 天)和 ATCA(t1/2 = 544 小时,23 天)相比,猪死后血液中的氯化萘浓度迅速下降(t1/2 = 34.3 小时)。死后血液中的 CN 不稳定性在 RT(t1/2 = 10.7 小时)和 HBT(t1/2 = 6.6 小时)时增加。在所有储存条件下,SCN- 和 ATCA 都比 CN 更稳定。在猪的尸体中,SCN- 和 ATCA 的 t1/2s 分别为 15 天和 23 天。虽然 SCN- 和 ATCA 的 t1/2s 都相对较长,但 SCN- 的内源性水平比 ATCA 的变化要大得多:结论:虽然仍有问题有待解答,但 ATCA 是氯化萘中毒最有效的法医标志物(即 ATCA 的半衰期最长、高于基线水平的增幅最大、背景浓度最稳定)。
{"title":"Can the cyanide metabolite, 2-aminothiazoline-4-carboxylic acid, be used for forensic verification of cyanide poisoning?","authors":"Abdullah H Alluhayb, Carter Severance, Tara Hendry-Hofer, Vikhyat S Bebarta, Brian A Logue","doi":"10.1007/s11419-024-00690-4","DOIUrl":"10.1007/s11419-024-00690-4","url":null,"abstract":"<p><strong>Purpose: </strong>Forensic verification of cyanide (CN) poisoning by direct CN analysis in postmortem blood is challenging due to instability of CN in biological samples. CN metabolites, thiocyanate (SCN<sup>-</sup>) and 2-aminothiazoline-4-carboxylic acid (ATCA), have been proposed as more stable biomarkers, yet it is unclear if either is appropriate for this purpose. In this study, we evaluated the behavior of CN biomarkers in postmortem swine and postmortem blood to determine which serves as the best biomarker of CN exposure.</p><p><strong>Methods: </strong>CN, SCN<sup>-</sup>, and ATCA were measured in postmortem swine (N = 8) stored at 4 °C and postmortem blood stored at 25 °C (room temperature, RT) and 37 °C (typical human body temperature, HBT).</p><p><strong>Results: </strong>Following CN poisoning, the concentration of each CN biomarker increased well above the baseline. In postmortem swine, CN concentrations declined rapidly (t<sub>1/2</sub> = 34.3 h) versus SCN<sup>-</sup> (t<sub>1/2</sub> = 359 h, 15 days) and ATCA (t<sub>1/2</sub> = 544 h, 23 days). CN instability in postmortem blood increased at RT (t<sub>1/2</sub> = 10.7 h) and HBT (t<sub>1/2</sub> = 6.6 h). SCN<sup>-</sup> and ATCA were more stable than CN at all storage conditions. In postmortem swine, the t<sub>1/2</sub>s of SCN<sup>-</sup> and ATCA were 15 and 23 days, respectively. While both the t1/2s of SCN<sup>-</sup> and ATCA were relatively lengthy, endogenous levels of SCN<sup>-</sup> were much more variable than ATCA.</p><p><strong>Conclusion: </strong>While there are still questions to be answered, ATCA was the most adept forensic marker of CN poisoning (i.e., ATCA produced the longest half-life, the largest increase above baseline levels, and most stable background concentrations).</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"221-231"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911252","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
Complementary information concerning the suspected interindividual transmission of GW1516, a substance prohibited in sport, through intimate contact: a case report. 关于疑似通过亲密接触在个体间传播体育禁用物质 GW1516 的补充信息:病例报告。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-05-05 DOI: 10.1007/s11419-024-00689-x
J Breuer, A M Garzinsky, A Thomas, E Nieschlag, S Kliesch, M Fedoruk, H Geyer, M Thevis

Purpose: Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) in the context of sports drug testing programs. Transfer of drug residues via unprotected intercourse is a conceivable scenario but scientific data and authentic case reports are scarce. Herein, investigations into two AAFs with the peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 are reported and discussed.

Methods: To probe for a contamination scenario involving sexual intercourse, two assays were used to determine semenogelin in human urine, with one employing an immunochromatographic lateral flow approach and another based on liquid chromatography-tandem mass spectrometry. Further, drug-residue testing using patients' ejaculate was conducted by utilizing liquid chromatography in conjunction with a triple quadrupole mass spectrometer, followed by re-analysis of suspect samples (i.e., samples indicating the presence of relevant compounds) using high resolution/high mass accuracy mass spectrometry.

Results: In one case, but not the other, the possibility of intimate contact as the source of the AAF was confirmed after a thorough investigation of potential contamination scenarios. Subsequent research revealed analytical evidence for the presence of seminal fluid in one of the female athlete's doping control urine samples, and the analysis of clinical ejaculate specimens provided first data on an authentic concentration level of GW1516 and its metabolites in human seminal fluid.

Conclusions: The combined facts substantiate the possibility of an AAF caused by unprotected sexual intercourse and the plausibility of the case-related arguments.

目的:在体育药物检测项目中,在出现所谓的不良分析结果(AAF)的情况下,无意和/或不知情地接触到药物和药物残留一直是人们经常争论的问题。通过无保护措施的性交转移药物残留是一种可以想象的情况,但科学数据和真实案例报告却很少。本文报告并讨论了与过氧化物酶体增殖激活受体δ(PPARδ)激动剂 GW1516 有关的两例 AAF 调查:方法:为了探究涉及性交的污染情况,我们使用了两种检测方法来测定人体尿液中的精蛋白硒,其中一种采用免疫层析侧流法,另一种基于液相色谱-串联质谱法。此外,还利用液相色谱法和三重四极杆质谱仪对患者的射精进行了药物残留检测,然后利用高分辨率/高质谱精度质谱法对可疑样本(即表明存在相关化合物的样本)进行了重新分析:结果:在对潜在的污染情况进行彻底调查后,确认了亲密接触是 AAF 来源的可能性,而不是另一种情况。随后的研究揭示了其中一名女运动员的兴奋剂控制尿样中存在精液的分析证据,对临床射精标本的分析首次提供了人体精液中 GW1516 及其代谢物真实浓度水平的数据:综合事实证明了无保护性交导致 AAF 的可能性以及与案例相关论据的可信性。
{"title":"Complementary information concerning the suspected interindividual transmission of GW1516, a substance prohibited in sport, through intimate contact: a case report.","authors":"J Breuer, A M Garzinsky, A Thomas, E Nieschlag, S Kliesch, M Fedoruk, H Geyer, M Thevis","doi":"10.1007/s11419-024-00689-x","DOIUrl":"10.1007/s11419-024-00689-x","url":null,"abstract":"<p><strong>Purpose: </strong>Inadvertent and/or unknowing exposure to drugs and drug residues has been frequently debated in situations of so-called adverse analytical finding (AAF) in the context of sports drug testing programs. Transfer of drug residues via unprotected intercourse is a conceivable scenario but scientific data and authentic case reports are scarce. Herein, investigations into two AAFs with the peroxisome proliferator-activated receptor delta (PPARδ) agonist GW1516 are reported and discussed.</p><p><strong>Methods: </strong>To probe for a contamination scenario involving sexual intercourse, two assays were used to determine semenogelin in human urine, with one employing an immunochromatographic lateral flow approach and another based on liquid chromatography-tandem mass spectrometry. Further, drug-residue testing using patients' ejaculate was conducted by utilizing liquid chromatography in conjunction with a triple quadrupole mass spectrometer, followed by re-analysis of suspect samples (i.e., samples indicating the presence of relevant compounds) using high resolution/high mass accuracy mass spectrometry.</p><p><strong>Results: </strong>In one case, but not the other, the possibility of intimate contact as the source of the AAF was confirmed after a thorough investigation of potential contamination scenarios. Subsequent research revealed analytical evidence for the presence of seminal fluid in one of the female athlete's doping control urine samples, and the analysis of clinical ejaculate specimens provided first data on an authentic concentration level of GW1516 and its metabolites in human seminal fluid.</p><p><strong>Conclusions: </strong>The combined facts substantiate the possibility of an AAF caused by unprotected sexual intercourse and the plausibility of the case-related arguments.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"248-254"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854419","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
Detection and quantification of etomidate and metomidate in human hairs by ultraperformance liquid chromatography with triple quadrupole mass spectrometry (UPLC-MS/MS). 利用超高效液相色谱-三重四极杆质谱法(UPLC-MS/MS)检测和定量人类毛发中的依托咪酯和美托咪酯。
IF 2.8 4区 医学 Q2 TOXICOLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-19 DOI: 10.1007/s11419-023-00678-6
Yinyin Dai, Xiaolong Zhang, Kundi Zhao, Yue Wang, Jinlei Liu, Jie Gu, Huiru Bai, Koutaro Hasegawa, Amin Wurita

Purpose: Intravenous narcotic agents, such as etomidate and metomidate, has been widely spread and abused in the world, including in Korea and China; thus, it is important to establish validated and sensitive analytical method for these compounds. Human hair as a biological sample has various advantages, including a wide detection window of drugs, compared to other typical samples, such as urine and blood in investigation. The purpose of this communication is to develop a reliable and useful method for the simultaneous detection and quantification of etomidate and metomidate in human hair samples by ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry (UPLC-MS/MS), and to apply it for authentic samples in abuse cases.

Methods: The hair samples were washed with a detergent solution, followed by with water and acetone. After drying, they were cut into approximately 2 mm sections and then ground to powder by a low-temperature grinder. The 20 mg of hair powder plus internal standard in 1 mL of methanol was vortexed and then centrifuged to obtain the supernatant layer, followed by subjecting to analysis.

Results: The coefficient of determination (r2) values of the calibration curves of etomidate and metomidate in the hair samples were both more than 0.99 in the range of 1-500 ng/mg and 1-500 pg/mg, respectively. The limits of detection and lower limits of quantification were 0.5 and 1 pg/mg, respectively, for the both target compounds. Other tested validation data were all satisfactory. Etomidate and metomidate could be detected in the all hair samples and cigarette oil, which were seized by the police. The concentrations of etomidate and metomidate obtained from 10 samples from suspects were 5.48-45.7 ng/mg and 3.60-377 pg/mg, respectively. The concentrations of etomidate and metomidate in the cigarette oil were 95.8 μg/mg and 2.8 μg/mg, respectively.

Conclusions: In this study, a simple and reliable analytical method for etomidate and metomidate in the human hair has been established. To the best of our knowledge, this is the first report to establish a method for the simultaneous detection and quantification of etomidate and metomidate in the human hair, and to apply it to authentic samples seized in authentic cases.

目的:静脉注射麻醉剂(如依托咪酯和甲氧苄啶等)已在全球(包括韩国和中国)广泛传播和滥用;因此,建立针对这些化合物的有效、灵敏的分析方法非常重要。与其他典型样本(如尿液和血液)相比,人类毛发作为生物样本具有多种优势,包括药物检测窗口宽。本文旨在开发一种可靠实用的方法,利用超高效液相色谱结合三重四极杆质谱法(UPLC-MS/MS)同时检测和定量人体毛发样本中的依托咪酯和安托咪酯,并将其应用于滥用药物案件中的真实样本:方法:用洗涤剂溶液清洗头发样本,然后用水和丙酮清洗。干燥后,将头发切成约 2 毫米的小段,然后用低温研磨机将其研磨成粉末。将 20 毫克毛发粉末和内标物加入 1 毫升甲醇中,涡旋后离心,得到上清层,然后进行分析:头发样品中依托咪酯和美托咪酯的校准曲线在 1-500 纳克/毫克和 1-500 皮克/毫克范围内的测定系数(r2)均大于 0.99。两种目标化合物的检测限和定量下限分别为 0.5 和 1 皮克/毫克。其他测试验证数据均令人满意。在警方查获的所有毛发样本和香烟油中都能检测到依托咪酯和安托咪酯。从 10 份嫌疑人样本中检测到的依托咪酯和安托咪酯的浓度分别为 5.48-45.7 纳克/毫克和 3.60-377 皮克/毫克。香烟油中依托咪酯和安托咪酯的浓度分别为 95.8 μg/mg 和 2.8 μg/mg:本研究建立了一种简单可靠的人体毛发中依托咪酯和安托咪酯的分析方法。据我们所知,这是第一份建立同时检测和定量人体毛发中依托咪酯和安托咪酯的方法,并将其应用于在真实案件中缴获的真实样本的报告。
{"title":"Detection and quantification of etomidate and metomidate in human hairs by ultraperformance liquid chromatography with triple quadrupole mass spectrometry (UPLC-MS/MS).","authors":"Yinyin Dai, Xiaolong Zhang, Kundi Zhao, Yue Wang, Jinlei Liu, Jie Gu, Huiru Bai, Koutaro Hasegawa, Amin Wurita","doi":"10.1007/s11419-023-00678-6","DOIUrl":"10.1007/s11419-023-00678-6","url":null,"abstract":"<p><strong>Purpose: </strong>Intravenous narcotic agents, such as etomidate and metomidate, has been widely spread and abused in the world, including in Korea and China; thus, it is important to establish validated and sensitive analytical method for these compounds. Human hair as a biological sample has various advantages, including a wide detection window of drugs, compared to other typical samples, such as urine and blood in investigation. The purpose of this communication is to develop a reliable and useful method for the simultaneous detection and quantification of etomidate and metomidate in human hair samples by ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry (UPLC-MS/MS), and to apply it for authentic samples in abuse cases.</p><p><strong>Methods: </strong>The hair samples were washed with a detergent solution, followed by with water and acetone. After drying, they were cut into approximately 2 mm sections and then ground to powder by a low-temperature grinder. The 20 mg of hair powder plus internal standard in 1 mL of methanol was vortexed and then centrifuged to obtain the supernatant layer, followed by subjecting to analysis.</p><p><strong>Results: </strong>The coefficient of determination (r<sup>2</sup>) values of the calibration curves of etomidate and metomidate in the hair samples were both more than 0.99 in the range of 1-500 ng/mg and 1-500 pg/mg, respectively. The limits of detection and lower limits of quantification were 0.5 and 1 pg/mg, respectively, for the both target compounds. Other tested validation data were all satisfactory. Etomidate and metomidate could be detected in the all hair samples and cigarette oil, which were seized by the police. The concentrations of etomidate and metomidate obtained from 10 samples from suspects were 5.48-45.7 ng/mg and 3.60-377 pg/mg, respectively. The concentrations of etomidate and metomidate in the cigarette oil were 95.8 μg/mg and 2.8 μg/mg, respectively.</p><p><strong>Conclusions: </strong>In this study, a simple and reliable analytical method for etomidate and metomidate in the human hair has been established. To the best of our knowledge, this is the first report to establish a method for the simultaneous detection and quantification of etomidate and metomidate in the human hair, and to apply it to authentic samples seized in authentic cases.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":"232-241"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491092","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
期刊
Forensic Toxicology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1