{"title":"Analysis of vaporized caffeine in smoke from e-cigarettes using liquid chromatography-tandem mass spectrometry and clarification of minor components.","authors":"Makoto Takada, Suzuna Saruwatari, Yutaro Yanagita, Junpei Mutoh, Hajime Harada, Naoya Kishikawa, Takashi Kitahara, Naotaka Kuroda, Mitsuhiro Wada","doi":"10.1007/s11419-022-00636-8","DOIUrl":"10.1007/s11419-022-00636-8","url":null,"abstract":"<p><strong>Purpose: </strong>Electronic cigarettes (e-cigarettes) are used widely, and e-cigarettes containing caffeine (Caf) have recently become commercially available. However, no risk evaluation of these Caf-containing products has been performed to date. Such an evaluation requires a sensitive analytical method for quantifying Caf in smoke from e-cigarettes. The aim of this study was to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying vaporized Caf from commercially available e-cigarettes, and to determine minor components related to Caf in cigarette smoke extract (CSE).</p><p><strong>Methods: </strong>A sampling system for Caf using a suction pump was designed and sampling conditions were optimized.</p><p><strong>Results: </strong>The optimized LC-MS/MS conditions allowed the sensitive determination of Caf in smoke with a limit of detection of 0.03 ng/mL at a signal-to-noise ratio of 3. The method was applied to CSEs from five e-cigarette products and the concentration of Caf ranged from 0.894 ± 0.090 to 3.32 ± 0.14 μg/mL smoke (n = 3). Additionally, minor components related to Caf, such as theobromine, theophylline, and paraxanthine, were detected in CSE and in e-liquid at very low concentrations, indicating that they were impurities in e-liquid and vaporized along with Caf.</p><p><strong>Conclusion: </strong>This is the first report to determine the concentration of vaporized Caf using an LC-MS/MS method and to clarify several minor components in smoke from e-cigarettes.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"135-141"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9281779","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}
Hunter D J Webb, David B Finlay, Shuli Chen, Andrea J Vernall, Eric Sparkes, Samuel D Banister, Rhonda J Rosengren, Michelle Glass
{"title":"Characterisation of AMB-FUBINACA metabolism and CB<sub>1</sub>-mediated activity of its acid metabolite.","authors":"Hunter D J Webb, David B Finlay, Shuli Chen, Andrea J Vernall, Eric Sparkes, Samuel D Banister, Rhonda J Rosengren, Michelle Glass","doi":"10.1007/s11419-022-00649-3","DOIUrl":"https://doi.org/10.1007/s11419-022-00649-3","url":null,"abstract":"<p><strong>Purpose: </strong>AMB-FUBINACA is a synthetic cannabinoid receptor agonist (SCRA) which is primarily metabolised by hepatic enzymes producing AMB-FUBINACA carboxylic acid. The metabolising enzymes associated with this biotransformation remain unknown. This study aimed to determine if AMB-FUBINACA metabolism could be reduced in the presence of carboxylesterase (CES) inhibitors and recreational drugs commonly consumed with it. The affinity and activity of the AMB-FUBINACA acid metabolite at the cannabinoid type-1 receptor (CB<sub>1</sub>) was investigated to determine the activity of the metabolite.</p><p><strong>Methods: </strong>The effect of CES1 and CES2 inhibitors, and delta-9-tetrahydrocannabinol (Δ<sup>9</sup>-THC) on AMB-FUBINACA metabolism were determined using both human liver microsomes (HLM) and recombinant carboxylesterases. Radioligand binding and cAMP assays comparing AMB-FUBINACA and AMB-FUBINACA acid were carried out in HEK293 cells expressing human CB<sub>1</sub>.</p><p><strong>Results: </strong>AMB-FUBINACA was rapidly metabolised by HLM in the presence and absence of NADPH. Additionally, CES1 and CES2 inhibitors both significantly reduced AMB-FUBINACA metabolism. Furthermore, digitonin (100 µM) significantly inhibited CES1-mediated metabolism of AMB-FUBINACA by ~ 56%, while the effects elicited by Δ<sup>9</sup>-THC were not statistically significant. AMB-FUBINACA acid produced only 26% radioligand displacement consistent with low affinity binding. In cAMP assays, the potency of AMB-FUBINACA was ~ 3000-fold greater at CB<sub>1</sub> as compared to the acid metabolite.</p><p><strong>Conclusions: </strong>CES1A1 was identified as the main hepatic enzyme responsible for the metabolism of AMB-FUBINACA to its less potent carboxylic acid metabolite. This biotransformation was significantly inhibited by digitonin. Since other xenobiotics may also inhibit similar SCRA metabolic pathways, understanding these interactions may elucidate why some users experience high levels of harm following SCRA use.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"114-125"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9849163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266036","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}
Benedicte Lelievre, Vincent Dupont, Celine Buchaillet, Nathalie Jousset, Marie Deguigne, Vincent Cirimele
{"title":"Correction to: Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine.","authors":"Benedicte Lelievre, Vincent Dupont, Celine Buchaillet, Nathalie Jousset, Marie Deguigne, Vincent Cirimele","doi":"10.1007/s11419-022-00648-4","DOIUrl":"https://doi.org/10.1007/s11419-022-00648-4","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"185"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9164337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of degradation products of nerve agents in biological fluids by ion chromatography-tandem mass spectrometry.","authors":"Mai Otsuka, Hajime Miyaguchi","doi":"10.1007/s11419-022-00633-x","DOIUrl":"https://doi.org/10.1007/s11419-022-00633-x","url":null,"abstract":"<p><strong>Purpose: </strong>The detection of hydrolysis products of nerve agents (alkyl methylphosphonic acids; RMPAs) in biological samples from victims is important to confirm exposure to nerve agents. However, analysis of RMPAs is difficult due to their high hydrophilicity. The aim of this study was to develop ion chromatography-tandem mass spectrometry (IC-MS/MS) methods using commercially available equipment and columns to analyze RMPAs in human urine and serum with high sensitivity and without using complicate techniques.</p><p><strong>Methods: </strong>A Dionex IonPac AS11-HC anion-exchange column was used to analyze six RMPAs (MPA, EMPA, IMPA, <sup>i</sup>BuMPA, CHMPA, and PMPA). For pretreatments of biological fluids, we developed two pretreatment methods (Method 1: dilution and ultrafiltration; Method 2: removal of chloride ions with Ag cartridges).</p><p><strong>Results: </strong>Six RMPAs including highly hydrophilic methylphosphonic acid and ethyl methylphosphonic acid could be analyzed with sufficient retention times and peak shape. The detection limits of RMPAs were improved using Dionex OnGuard II Ba/Ag/H cartridges and MetaSEP IC-Ag cartridges (urine: 0.5-5 ng/mL; serum: 1-5 ng/mL). These methods were also applied to the test samples for the Organisation for the Prohibition of Chemical Weapons Biomedical Proficiency Tests.</p><p><strong>Conclusions: </strong>RMPAs could be sufficiently analyzed by IC-MS/MS. In addition, the limits of detection were superior to those obtained in our previous study involving LC-MS/MS or derivatization-LC-MS/MS method. For analysis of biological samples, an appropriate pretreatment method can be chosen according to the amount of sample available for analysis and expected RMPA concentrations.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"71-80"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9281780","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}
Yue Wang, Lifeng Han, Liye Yi, Jinlei Liu, Shi Qiu, Jie Gu, Huiru Bai, Jun Li, Amin Wurita, Koutaro Hasegawa
{"title":"Newly emerging synthetic cannabinoid ADB-4en-PINACA: its identification and quantification in an authentic human hair sample by GC-MS/MS.","authors":"Yue Wang, Lifeng Han, Liye Yi, Jinlei Liu, Shi Qiu, Jie Gu, Huiru Bai, Jun Li, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-022-00643-9","DOIUrl":"https://doi.org/10.1007/s11419-022-00643-9","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"173-178"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9281786","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}
Karen Rafaela Gonçalves de Araujo, André Luis Fabris, Luiz F Neves Júnior, Júlio de Carvalho Ponce, Alexandre Learth Soares, José Luiz Costa, Mauricio Yonamine
{"title":"The mystery behind the apprehensions of the selective cannabinoid receptor type-2 agonist BZO-HEXOXIZID (MDA-19) as a drug of abuse.","authors":"Karen Rafaela Gonçalves de Araujo, André Luis Fabris, Luiz F Neves Júnior, Júlio de Carvalho Ponce, Alexandre Learth Soares, José Luiz Costa, Mauricio Yonamine","doi":"10.1007/s11419-022-00646-6","DOIUrl":"https://doi.org/10.1007/s11419-022-00646-6","url":null,"abstract":"<p><strong>Purpose: </strong>MDA-19 or BZO-HEXOXIZID (N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-benzohydrazide), in a more recent nomenclature, was first synthesized in 2008 as a selective type-2 cannabinoid receptor (CB2) agonist due to its potential to treat neuropathic pain. In Brazil, this substance was identified in a series of 53 apprehensions between September 2021 and February 2022. Nevertheless, what intrigues toxicologists is that BZO-HEXOXIZID does not exert significant type-1 cannabinoid receptor (CB1) agonism-which is responsible for the well-known psychoactivity of Δ-9-tetrahydrocannabinol. Thus, the objective of this work is to report the first apprehension and identification of BZO-HEXOXIZID in Brazil and to discuss pharmacologically the possible reasons why a CB2 agonist has been incorporated to the illicit market.</p><p><strong>Methods: </strong>Suspected seized samples were sent to the Laboratory of the Scientific Police of the State of Sao Paulo. After the screening, samples were confirmed for the presence of BZO-HEXOXIZID using chromatography gas-mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance techniques.</p><p><strong>Results: </strong>Of the 53 samples analyzed, 25 contained only BZO-HEXOXIZID and 28 with mixtures, of which 11 with the CB1 agonist ADB-BUTINACA. Other substances were found in association such as cocaine and caffeine.</p><p><strong>Conclusions: </strong>BZO-HEXOXIZID was detected in a series of seized materials for the first time in Brazil. Nevertheless, there are still unanswered questions regarding the use of this selective CB2 agonist as a drug of abuse.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"142-150"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9281787","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":"Exposure to high concentrations of carbon dioxide during transporting a cadaver preserved with dry ice inside an ambulance vehicle.","authors":"Ibuki Oyama, Yasuhisa Tajima, Toshiyuki Ojima, Akiyoshi Iida","doi":"10.1007/s11419-022-00644-8","DOIUrl":"https://doi.org/10.1007/s11419-022-00644-8","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"179-182"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9459683","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":"Correction to: A potential of methoxpropamine to be a widespread recreational drug: it blocks NMDA receptors and inhibits NMDA receptor-mediated synaptic transmission in a brain preparation of mice","authors":"T. Irie, D. Yamazaki, R. Kikura-Hanajiri","doi":"10.1007/s11419-022-00651-9","DOIUrl":"https://doi.org/10.1007/s11419-022-00651-9","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"186 - 186"},"PeriodicalIF":2.2,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48538031","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}
Kenneth B Chapman, Noud van Helmond, Jan Willem Kallewaard, Kris C Vissers, Kiran V Patel, Soriaya Motivala, Jonathan M Hagedorn, Timothy R Deer, David M Dickerson
{"title":"An Anatomy-Informed, Novel Technique for S1 Dorsal Root Ganglion Stimulation Lead Placement.","authors":"Kenneth B Chapman, Noud van Helmond, Jan Willem Kallewaard, Kris C Vissers, Kiran V Patel, Soriaya Motivala, Jonathan M Hagedorn, Timothy R Deer, David M Dickerson","doi":"10.1093/pm/pnac062","DOIUrl":"10.1093/pm/pnac062","url":null,"abstract":"<p><strong>Objective: </strong>A heightened and organized understanding of sacral anatomy could potentially lead to a more effective and safe method of dorsal root ganglion stimulation (DRG-S) lead placement. The aim of this technical note is to describe a standardized access method for S1 DRG-S lead placement.</p><p><strong>Design: </strong>Technical note.</p><p><strong>Methods: </strong>The described approach utilizes alignment of the lumbosacral prominence and is measurement-based, allowing for standardized sacral access, even when visualization is suboptimal. The medial-to-lateral needle trajectory is designed to limit interaction with the sensitive neural structures and allows for a more parallel orientation of the lead to the DRG and nerve root.</p><p><strong>Conclusions: </strong>The described technique potentially improves the safety of S1 DRG-S lead placement. The parallel lead orientation to the DRG may also increase efficacy while lowering energy requirements.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"26 1","pages":"1750-1756"},"PeriodicalIF":0.0,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74365487","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}
Dayanira Paniagua, Kendall Crowns, Michelle Montonera, Anne Wertheimer, A. Alagón, L. Boyer
{"title":"Correction to: Postmortem histopathology and detection of venom by ELISA following suicide by cobra (Naja kaouthia) envenomation","authors":"Dayanira Paniagua, Kendall Crowns, Michelle Montonera, Anne Wertheimer, A. Alagón, L. Boyer","doi":"10.1007/s11419-022-00642-w","DOIUrl":"https://doi.org/10.1007/s11419-022-00642-w","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 1","pages":"183 - 183"},"PeriodicalIF":2.2,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49652702","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}