Forensic Toxicology最新文献

{"title":"Quantification of olanzapine and its three metabolites by liquid chromatography-tandem mass spectrometry in human body fluids obtained from four deceased, and confirmation of the reduction from olanzapine N-oxide to olanzapine in whole blood in vitro.","authors":"Hideki Nozawa, Kayoko Minakata, Koutaro Hasegawa, Itaru Yamagishi, Naotomo Miyoshi, Masako Suzuki, Takuya Kitamoto, Minako Kondo, Kanako Watanabe, Osamu Suzuki","doi":"10.1007/s11419-023-00662-0","DOIUrl":"10.1007/s11419-023-00662-0","url":null,"abstract":"<p><strong>Purpose: </strong>Quantification of olanzapine (OLZ) and its metabolites such as N-desmethylolanzapine (DM-O), 2-hydroxymethylolanzapine (2H-O) and olanzapine N-oxide (NO-O) in five kinds of human body fluids including whole blood by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) has been presented; the quantification methods were carefully devised and validated using the matrix-matched calibration and standard addition methods.</p><p><strong>Methods: </strong>OLZ and its three metabolites were extracted from 40 μL each of body fluids by two-step liquid-liquid separations. The samples and reagents were pre-cooled in a container filled with ice for the extraction because of the thermal instability of OLZ and its three metabolites especially in whole blood.</p><p><strong>Results: </strong>The limits of quantification (LOQs) of OLZ and 2H-O were 0.05 ng/mL and those of DM-O and NO-O were 0.15 ng/mL in whole blood and urine, respectively. The concentrations of OLZ and its metabolites in heart whole blood, pericardial fluid, stomach contents, bile and urine were determined for two cadavers and those in whole blood and urine for the other two cadavers. The reduction from NO-O to OLZ was observed at 25 ℃ in whole blood in vitro.</p><p><strong>Conclusions: </strong>To our knowledge, this is the first report on the quantification of metabolites of olanzapine in the authentic human body fluids by LC-MS/MS as well as on the confirmation of in vitro reduction from NO-O to OLZ in whole blood that seems to have induced the quick decrease of NO-O.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"318-328"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741238","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":"Suicidal intoxication with mercury chloride.","authors":"Sławomir Majdanik,&nbsp;Barbara Potocka-Banaś,&nbsp;Sebastian Glowinski,&nbsp;Sylwester Luzny","doi":"10.1007/s11419-022-00653-7","DOIUrl":"https://doi.org/10.1007/s11419-022-00653-7","url":null,"abstract":"<p><strong>Purpose: </strong>Poisoning with elemental metals and metallic compounds was much more frequent in the past, and was related, among other things, to lifestyle and the lack of appropriate toxicological diagnostics. One example is mercury, which is being gradually eliminated but still has many different applications as a pure metal or in the form of various compounds. The paper presents a case of suicidal poisoning with mercury chloride (corrosive sublimate).</p><p><strong>Methods: </strong>Forensic and toxicological tests including inductively coupled plasma mass spectrometry (ICP-MS) were at the Department of Forensic Medicine, PMU in Szczecin.</p><p><strong>Results: </strong>The patient before death had a range of symptoms such as epigastric pain, vomiting of the stomach contents, central cyanosis with tachycardia, tremors, severe shortness of breath with wheezing, difficulty swallowing, slurred speech, rales in the lungs, and diarrhea. The concentration of mercury measured by ICP-MS was 191 mg/L for a blood sample collected antemortem, and 147 mg/L for a blood sample collected at autopsy. Both concentrations of mercury are regarded as lethal. The post-mortem examination revealed signs of extensive thrombotic necrosis in some internal organs.</p><p><strong>Conclusions: </strong>Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. It can produce a range of toxic effects, including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. The presented case of fatal poisoning with mercury chloride, due to the type of agent used, is now interesting in toxicological practice.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"304-308"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732257","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":"Urinary profiles of methoxyphenamine and its metabolite after inhalation of methoxyphenamine smoke in humans: aiming to distinguish between active and passive exposure.","authors":"Haruka Morinaka, Asuka Kaizaki-Mitsumoto, Hokuto Morohoshi, Naoki Uchida, Satoshi Numazawa","doi":"10.1007/s11419-022-00658-2","DOIUrl":"10.1007/s11419-022-00658-2","url":null,"abstract":"<p><strong>Purpose: </strong>Methamphetamine (METH) is commonly abused through smoking. However, the lack of evidence regarding differences in urinary METH excretion after its active and passive inhalation has resulted in complications where the accused claims passive exposure. This study aimed to determine the differences in urinary excretion after active and passive inhalation of the drug, using methoxyphenamine (MPA) as a model for METH.</p><p><strong>Methods: </strong>Body temperature and locomotor activity were measured in mice as indicators of central nervous system toxicity. Six healthy adult male subjects were exposed to passive or active inhalation of MPA smoke in a small room, and urine samples were taken. MPA concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>There were no signs of toxicity in mice exposed to MPA smoke, ensuring the safety of the clinical study. Urinary MPA concentrations were significantly lower with passive inhalation compared with those of active inhalation. The maximum urinary MPA concentration in passive inhalation was 13.4 ng/mL, which was 1/60 of active inhalation with 800 ng/mL. The urinary excretion in passive inhalation until 24 h was 8.21 μg, which was 1/76 of active inhalation with 625 μg.</p><p><strong>Conclusions: </strong>Since METH and MPA are expected to be excreted similarly, urinary METH concentrations in passively exposed persons are expected to be lower than the cutoff value of the screening kit. If the urine screening test is positive, the suspect should be considered a METH user.</p><p><strong>Trial registration number: </strong>jRCTs031210604, registration date: Feb. 9, 2022.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"230-240"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9723305","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":"Emerging trends in methaqualone and analogues abuse: insights from online forums.","authors":"Patryk Kuropka, Marcin Zawadzki, Paweł Szpot","doi":"10.1007/s11419-023-00665-x","DOIUrl":"10.1007/s11419-023-00665-x","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"329-331"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725380","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 Novichok agents in human urine by hydrophilic interaction liquid chromatography-tandem mass spectrometry.","authors":"Mai Otsuka,&nbsp;Akinori Yamaguchi,&nbsp;Hajime Miyaguchi","doi":"10.1007/s11419-022-00656-4","DOIUrl":"https://doi.org/10.1007/s11419-022-00656-4","url":null,"abstract":"<p><strong>Purpose: </strong>The detection of hydrolysis products of Novichok agents in biological samples from victims is important for confirming exposure to these agents. However, Novichok agents are new class of nerve agent and there have been only few reports on analyses of Novichok agent degradation products. Here, we developed hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS) methods to detect Novichok agent degradation products in human urine with simple pretreatment and high sensitivity.</p><p><strong>Methods: </strong>A Poroshell 120 HILIC-Z column was used to analyze six Novichok agent degradation products. For urine samples, we used a simple pretreatment method, which consisted of deproteinization with acetonitrile and microfiltration. We calculated the pK_a values of the OH groups, the log P values, and the molecular weights to investigate the difference in chromatographic behaviors of the Novichok agent degradation products and the degradation products of conventional nerve agents.</p><p><strong>Results: </strong>Six Novichok agent degradation products, including N-(bis-(diethylamino)methylidene)-methylphosphonamidic acid (MPGA), which could not be detected by our previous method, could be analyzed with sufficient peak shape and mutual separation. The detection limits of six Novichok agent degradation products were sufficiently low (1-50 ng/mL) and the calibration curves showed sufficient linearity. The physicochemical parameters of Novichok agent degradation products were different from those of conventional nerve agent degradation products, and this explains the difference in chromatographic behaviors.</p><p><strong>Conclusion: </strong>Six Novichok agent degradation products were successfully analyzed by HILIC-MS/MS. Due to the absence of a derivatization step, throughput performance was higher than our previous derivatization-liquid chromatography-MS/MS method.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"221-229"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732262","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":"Acute, chronic, and post-mortem toxicity: a review focused on three different classes of new psychoactive substances.","authors":"Caio H P Rodrigues, Lívia S Mariotto, Jade S Castro, Paulo H Peruquetti, Newton C Silva-Junior, Aline T Bruni","doi":"10.1007/s11419-022-00657-3","DOIUrl":"10.1007/s11419-022-00657-3","url":null,"abstract":"<p><strong>Purpose: </strong>New psychoactive substances (NPS) are not controlled under the Single Convention on Narcotic Drugs of 1961 or the 1971 Convention, but they may pose a public health threat. Knowledge of the main properties and toxicological effects of these substances is lacking. According to the current Drugs Law (Law n. 11.343/2006), the Brazilian Surveillance Agency issues directives for forbidden substances in Brazil, and structural classes of synthetic cannabinoids, cathinones, and phenylethylamines are considered illicit drugs. Considering that data on these controlled substances are scattered, the main objective of this work was to collect and organize data to generate relevant information on the toxicological properties of NPS.</p><p><strong>Methods: </strong>We carried out a literature review collecting information on the acute, chronic, and post-mortem toxicity of these classes of NSP. We searched info in five scientific databases considering works from 2017 to 2021 and performed a statistical evaluation of the data.</p><p><strong>Results: </strong>Results have shown a general lack of studies in this field given that many NPS have not had their toxicity evaluated. We observed a significant difference in the volume of data concerning acute and chronic/post-mortem toxicity. Moreover, studies on the adverse effects of polydrug use are scarce.</p><p><strong>Conclusions: </strong>More in-depth information about the main threats involving NPS use are needed.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"187-212"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735576","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":"Liquid chromatography with tandem mass spectrometric method for determination of 425 drugs and poisons in dried blood spots and application to forensic cases.","authors":"Caixia Guo, Hui Yan, Wei Liu, Ping Xiang, Bin Di, Min Shen","doi":"10.1007/s11419-023-00659-9","DOIUrl":"10.1007/s11419-023-00659-9","url":null,"abstract":"<p><strong>Purpose: </strong>An analytical method using liquid chromatography with tandem mass spectrometry (LC-MS/MS) was established and validated for screening 425 drugs and poisons in dried blood spots (DBSs).</p><p><strong>Methods: </strong>Blood (20 μL) was spotted on Whatman FTA™ classic card to prepare DBS sample, then extracted with 150 μL methanol and analyzed by LC-MS/MS using a multiple reaction monitoring method.</p><p><strong>Results: </strong>The limit of detection of the compounds were 0.1-10 ng/mL. The values for recovery and matrix effect were 40.3-114.9% and 40.2-118.4%, respectively. This method was successfully applied to DBS samples from 105 humans suspected of drug poisoning, which was stored for 3-5 years at room temperature. Thirty-three kinds of drugs, including benzodiazepines, antipsychotics, antidepressants, antipyretic analgesics, non-steroidal anti-inflammatory drugs, antibiotics, antiepileptic drugs, new psychoactive drugs were confirmed in 102 cases, while no compound was detected in the other 3 cases. Estazolam, a benzodiazepine widely used in clinical practice as a sedative, hypnotic, and anti-anxiety drug, was the most frequently detected substance, occurring in 34.2% of the cases.</p><p><strong>Conclusions: </strong>Most drugs in DBS could still be detected after storage for 3-5 years, but ambroxol, zopiclone, carbofuran, chlorpyrifos, and valproic acid were not detectable after 3-5 years of storage at room temperature. The components measured in DBS were consistent with those measured in whole blood at the collection time, thereby confirming that DBS samples have the advantage of stable storage at room temperature.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"241-248"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971425","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":"Cannabidiol in urine is not a proof of CBD consumption-lesson learned from urine sample analysis in routine caseworks.","authors":"Marine Deville,&nbsp;Corinne Charlier","doi":"10.1007/s11419-022-00652-8","DOIUrl":"https://doi.org/10.1007/s11419-022-00652-8","url":null,"abstract":"<p><strong>Purpose: </strong>Cannabidiol (CBD) has been gaining popularity in recent years. Knowing that CBD products can contain more tetrahydrocannabinol (THC) than expected, interpretation of cannabinoids concentration in urine can be tricky, especially when low amounts of THC and CBD are found. Moreover, interpretation can also be difficult due to interindividual variation in pharmacokinetics. The objective of this work was to take a critical look at the data from our daily practice as a toxicology laboratory.</p><p><strong>Methods: </strong>We have collected results obtained in a first batch of 1074 urine samples submitted to cannabinoids analysis, and results of cannabinoids content of a second batch of 719 seized materials.</p><p><strong>Results: </strong>CBD was detected in 163 urine specimens (15%). Its concentration was higher than the limit of quantification of 5 ng/mL in 108 samples only (10% of the sampling population). Most of CBD-positive samples were associated with a high THC-COOH concentration (> 500 ng/mL in 63.8% of CBD-positive samples) suggesting only a few CBD consumers in our population. Cannabinoids composition of seized plant materials (drug type at first glance) revealed CBD in 110 of them (15% of the sampling population), with a concentration mostly below 1%. All of the resin samples were CBD positive, and contained more THC compared to flowers.</p><p><strong>Conclusions: </strong>We can conclude that urine samples from drug-type cannabis users contained a low amount of CBD, what was not described previously. These findings are useful for the interpretation of cannabinoids results in daily practice.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"213-220"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10091809","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":"Analytical characterization and differentiation between threo- and erythro-4-fluoroethylphenidate.","authors":"Miho Sakamoto, Toshinari Suzuki, Daisuke Teraoka, Kazue Tanaka, Yuki Saeki, Kiyoko Kishimoto, Machiko Nagashima, Jun'ichi Nakajima, Jin Suzuki, Akiko Inomata, Takako Moriyasu, Haruhiko Fukaya","doi":"10.1007/s11419-023-00664-y","DOIUrl":"10.1007/s11419-023-00664-y","url":null,"abstract":"<p><strong>Purpose: </strong>Methylphenidate analogs appeared on the drug market during the last years. Its analogs contain two chiral centers and, thus, have potential varying configurations (i.e., threo and erythro forms). This study presents the analytical characterization of 4-fluoroethylphenidate (4-FEP) and its differentiation between threo- and erythro-4-FEP.</p><p><strong>Methods: </strong>Analysis of the samples included high-performance liquid chromatography (HPLC), gas chromatography-electron ionization-mass spectrometry (GC-EI-MS), high-resolution mass spectrometry (HRMS) analyses, nuclear magnetic resonance (NMR) spectroscopy and X-ray crystal structure analysis.</p><p><strong>Results: </strong>NMR spectroscopic investigations confirmed the differences between threo- and erythro-4-FEP, and demonstrated that both isomers could be separated using HPLC and GC methods. Two samples obtained from one vendor in 2019 consisted of threo-4-FEP, whereas the other two samples obtained from a different vendor in 2020 consisted of a mixture of threo- and erythro-4-FEP.</p><p><strong>Conclusions: </strong>Several analytical approaches including HPLC, GC-EI-MS, HRMS analyses, NMR spectroscopy and X-ray crystal structure analysis enabled the unambiguous identification of threo- and erythro-4-FEP. The analytical data presented in this article will be useful for identifying threo- and erythro-4-FEP included in illicit products.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"272-286"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10093417","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":"Δ⁹-Tetrahydrocannabinol stimulation of estrogen receptor-positive MCF-7 breast cancer cell migration: Interfering interaction with the estrogenic milieu.","authors":"Shuso Takeda,&nbsp;Masayo Hirao-Suzuki,&nbsp;Hironori Aramaki,&nbsp;Kazuhito Watanabe","doi":"10.1007/s11419-022-00655-5","DOIUrl":"https://doi.org/10.1007/s11419-022-00655-5","url":null,"abstract":"<p><strong>Purpose: </strong>The effects of extended Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exposure on estrogen receptor-positive human breast cancer MCF-7 cells have been investigated; however, the effects of Δ⁹-THC exposure for a shorter duration remain unclear. In this study, we sought to study whether Δ⁹-THC stimulates the migration of MCF-7 cells under both estrogenic and estrogen-deprived conditions over a short period (approximately 6 h).</p><p><strong>Methods: </strong>MCF-7 cells were treated with Δ⁹-THC under estrogenic or estrogen-deprived conditions, and cell migration was subsequently analyzed.</p><p><strong>Results: </strong>Δ⁹-THC-stimulated migration of MCF-7 cells 6 h after exposure was only observed in the estrogen-deprived condition. However, Δ⁹-THC-mediated migration was counteracted under estrogenic conditions without affecting cell proliferation and estrogen receptor expression during this period.</p><p><strong>Conclusions: </strong>Δ⁹-THC can stimulate MCF-7 cell migration under estrogen-deprived conditions; however, there is an interfering interaction between Δ⁹-THC and the estrogenic milieu that influences the migration of MCF-7 cells.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"41 2","pages":"287-293"},"PeriodicalIF":2.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731646","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}