{"title":"Long-term stability of 24 synthetic cannabinoid metabolites spiked into whole blood and urine for up to 168 days, and the comparable study for the 6 metabolites in non-spiked real case specimens stored for 1-5 years.","authors":"Kayoko Minakata, Koutaro Hasegawa, Hideki Nozawa, Itaru Yamagishi, Naotomo Miyoshi, Masako Suzuki, Takuya Kitamoto, Minako Kondo, Kanako Watanabe, Osamu Suzuki","doi":"10.1007/s11419-022-00613-1","DOIUrl":"https://doi.org/10.1007/s11419-022-00613-1","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study is to investigate the stabilities of the 24 synthetic cannabinoid metabolites (SCMs) in blood and urine at various temperatures from - 30 to 37 ℃ stored for 1-168 days. In addition, experiments of stabilities at lower temperatures and for much longer duration have been performed as described below.</p><p><strong>Methods: </strong>The quantification was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The blank blood and urine spiked with SCMs and non-spiked real case (authentic) specimens were incubated at 37 ℃ up to 56 days and at 22, 4 or - 30 ℃ up to 168 days. The non-spiked authentic blood and urine specimens were also stored at - 30 or - 80 ℃ for 1, 3 or 5 years to investigate stabilities during very long time frames.</p><p><strong>Results: </strong>All the 24 SCMs were much more stable in urine than in blood at 37, 22 or 4 ℃. All 24 SCMs spiked into blood or urine were stable at - 30 ℃ for up to 168 days. The 6 SCMs in the authentic specimens exhibited long stabilities at - 30 or - 80 ℃ for 3-5 years. Some tendencies were observed according to the relation between the structures of SCMs and their stabilities.</p><p><strong>Conclusions: </strong>The long-term stabilities of 24 SCMs in spiked samples and those of 6 SCMs in the authentic specimens were examined using LC-MS/MS. SCMs were largely very stable and usable several years after storage at - 30 or - 80 ℃.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"289-301"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180143","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}
Benedicte Lelievre, Vincent Dupont, Celine Buchaillet, Nathalie Jousset, Marie Deguigne, Vincent Cirimele
{"title":"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/s11419-022-00628-8","DOIUrl":"https://doi.org/10.1007/s11419-022-00628-8","url":null,"abstract":"<p><strong>Purpose: </strong>Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest.</p><p><strong>Methods: </strong>Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection.</p><p><strong>Results: </strong>Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse.</p><p><strong>Conclusion: </strong>In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"383-392"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665232","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":"Micro-segmental hair analysis: detailed procedures and applications in forensic toxicology.","authors":"Kenji Kuwayama, Hajime Miyaguchi, Tatsuyuki Kanamori, Kenji Tsujikawa, Tadashi Yamamuro, Hiroki Segawa, Yuki Okada, Yuko T Iwata","doi":"10.1007/s11419-022-00619-9","DOIUrl":"https://doi.org/10.1007/s11419-022-00619-9","url":null,"abstract":"<p><strong>Purpose: </strong>Since the 1980s, the detection sensitivity of mass spectrometers has increased by improving the analysis of drugs in hair. Accordingly, the number of hair strands required for the analysis has decreased. The length of the hair segment used in the analysis has also shortened. In 2016, micro-segmental hair analysis (MSA), which cuts a single hair strand at a 0.4-mm interval corresponding to a hair growth length of approximately one day, was developed. The advantage of MSA is that the analytical results provide powerful evidence of drug use in the investigation of drug-related crimes and detailed information about the mechanism of drug uptake into hair. This review article focuses on the MSA technique and its applications in forensic toxicology.</p><p><strong>Methods: </strong>Multiple databases, such as SciFinder, PubMed, and Google, were utilized to collect relevant reports referring to MSA and drug analysis in hair. The experiences of our research group on the MSA were also included in this review.</p><p><strong>Results: </strong>The analytical results provide a detailed drug distribution profile in a hair strand, which is useful for examining the mechanism of drug uptake into hair in detail. Additionally, the analytical method has been used for various scenarios in forensic toxicology, such as the estimation of days of drug consumption and death.</p><p><strong>Conclusions: </strong>The detailed procedures are summarized so that beginners can use the analytical method in their laboratories. Moreover, some application examples are presented, and the limitations of the current analytical method and future perspectives are described.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"215-233"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10279615","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":"Non-fentanyl-derived synthetic opioids emerging during recent years.","authors":"Koutaro Hasegawa, Kayoko Minakata, Masako Suzuki, Osamu Suzuki","doi":"10.1007/s11419-022-00624-y","DOIUrl":"https://doi.org/10.1007/s11419-022-00624-y","url":null,"abstract":"<p><strong>Purpose: </strong>Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years. In this article, the recent abrupt changes in the situations of illicit synthetic opioid market and their current abuses are described.</p><p><strong>Methods: </strong>Various databases, such as SciFinder, Google, and Google Scholar, were utilized to collect relevant reports referring old but newly appearing synthetic opioids.</p><p><strong>Results: </strong>At the present time, there are several families of new synthetic opioids, which are not fentanyl derivatives; MT-45 and its analogs, benzamide and 2-phenylacetamide opioids (U-series opioids), and benzimidazole opioids. Most of the above substances had been developed in 1950s to 1970s, but had never been used as analgesic medicines, because of their severe adverse effects, such as respiratory depression, physical dependence, and resulting deaths. However, there is possibility that these drugs will become main illicit synthetic opioids in place of the fentanyl analogs during coming several years from this time.</p><p><strong>Conclusions: </strong>All of the above non-fentanyl-derived families had been developed 50-70 years ago to establish them as analgesic medicines, but had been unsuccessful. These drugs largely appeared in the illicit drug markets in North America, Europe, and Australia, during recent years. Pharmacological, toxicological, and metabolic studies are insufficient for benzamide and 2-phenylacetamide opioids, and are very scant especially for benzimidazole opioids. This time we should start studying pharmacotoxicology of the newly emerging synthetic opioids to alert forensic toxicologists in the world and to suppress their rapid and wide spread in the world.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"234-243"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689531","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":"2-Methoxyqualone, a new recreational drug, discovered from a package seized by the police: a preliminary report.","authors":"Hongkun Yang, Shuyun Wang, Haitao Qi, Jinlei Liu, Yue Wang, Jie Gu, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-022-00626-w","DOIUrl":"10.1007/s11419-022-00626-w","url":null,"abstract":"","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"414-416"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163271","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":"First liquid chromatography-high resolution mass spectrometry method for the determination of cocaine on banknote dust.","authors":"Teresa Cecchi, Elisa Santoni","doi":"10.1007/s11419-022-00627-9","DOIUrl":"https://doi.org/10.1007/s11419-022-00627-9","url":null,"abstract":"<p><strong>Purpose: </strong>Prevalence measures of sociological interest concerning cocaine presence on banknotes are fraught with (i) the extreme variability of its concentration (seven orders of magnitude); (ii) the high number of banknotes needed for the statistical significance. Banknote dust from counting machines from a large and representative number of banknotes in circulation in a specific area represents the most eligible sample to ascertain cocaine circulation. No chromatographic method is available in this respect. This study aims at developing the first analytical methodology for the determination of cocaine in banknote dust samples.</p><p><strong>Methods: </strong>This novel and straightforward approach consists of a simple methanol extraction followed by analytical determinations via ultra-high performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry.</p><p><strong>Results: </strong>Satisfactory analytical performance was obtained with a coefficient of determination of 0.996; maximum within-run and between-run precisions were, respectively, 1.85% and 5.20%. Limits of detection and quantification were, respectively, 3 and 9 ng/mL with an overall process efficiency of 93.2%. The method developed was successfully applied to 9 banknote dust samples from local banknote counter machines. The found concentrations ranged from 2.18E + 02 to 2.31E + 03 μg of cocaine per gram of banknote dust and varied only one order of magnitude, much less than cocaine concentration on banknotes.</p><p><strong>Conclusions: </strong>To have an idea of cocaine circulation in a geographical area, the sampling of banknote dust, compared to banknotes, consists of tremendous advantages in terms of statistical significance, higher cocaine concentrations, and lower variability: this is crucial from the sociological point of view.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"357-365"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163272","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":"Comparison of serum and whole blood concentrations in quetiapine overdose cases.","authors":"Takeshi Saito, Tomoatsu Tsuji, Akira Namera, Seiji Morita, Yoshihide Nakagawa","doi":"10.1007/s11419-022-00618-w","DOIUrl":"https://doi.org/10.1007/s11419-022-00618-w","url":null,"abstract":"<p><p>This study aimed to compare whole blood and serum concentrations of quetiapine in acute poisoning cases. Authentic whole blood and respective serum samples were routinely collected from patients diagnosed with blood poisoning at our University Hospital. Accordingly, whole blood and serum paired samples from nine patients (one male and eight female patients) were analyzed for quetiapine using liquid chromatography-mass spectrometry (LC-MS). Quetiapine concentrations in whole blood and serum samples ranged widely from 5.4 to 2780 ng/mL and 9.9 to 2500 ng/mL, respectively. The whole blood/serum concentration ratio was 0.5-1.1 and increased together with an increase in whole blood and serum quetiapine concentrations. The ratio was reversed at around 2500 ng/mL to > 1. Our findings suggest that whole blood concentrations are more useful than serum concentrations in diagnosing quetiapine poisonings.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"403-406"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163265","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":"Simultaneous determination of diquat and its two primary metabolites in rat plasma by ultraperformance liquid chromatography-tandem mass spectrometry and its application to the toxicokinetic study.","authors":"Zhengsheng Mao, Youjia Yu, Hao Sun, Chao Wu, Qiaoyan Jiang, Chunyan Chu, Chongwen Zhao, Yujie Zhou, Jinsong Zhang, Yue Cao, Feng Chen","doi":"10.1007/s11419-022-00623-z","DOIUrl":"https://doi.org/10.1007/s11419-022-00623-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop and validate an ultraperformance liquid chromatography-tandem mass spectrometry to simultaneously determine diquat (DQ) and its two primary metabolites in rat plasma and its application to the toxicokinetic study.</p><p><strong>Method: </strong>The chromatographic separation of DQ and its two primary metabolites was performed with hydrophilic interaction chromatography column by adding formic acid and ammonium acetate in mobile phase in stepwise elution mode. DQ and its two primary metabolites were detected by liquid chromatography-tandem mass spectrometry in positive mode.</p><p><strong>Results: </strong>The lower limit of quantification ranging from 0.3 to 3.0 ng/mL for DQ and its two primary metabolites was achieved by using only 50 μL of rat plasma. The maximum concentration (C<sub>max</sub>) was 977 ng/mL, half-life (t<sub>1/2</sub>) was 13.1 h, and area under the plasma concentration-time curve (AUC<sub>0-t</sub>) was 2770 h*ng/mL for DQ, C<sub>max</sub> was 47.1 ng/mL, t<sub>1/2</sub> was 25.1 h, and AUC<sub>0-t</sub> was 180 h·ng/mL for diquat monopyridone (DQ-M) and C<sub>max</sub> was 246 ng/mL, t<sub>1/2</sub> was 8.2 h, and AUC<sub>0-t</sub> was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively.</p><p><strong>Conclusions: </strong>The validated method was shown to be suitable for simultaneous determination of diquat and its two primary metabolites in rat plasma. This study is the first to study the toxicokinetics of DQ and its two primary metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"332-339"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163270","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}
Kelly Francisco da Cunha, Julia Martinelli Magalhães Kahl, Taís Regina Fiorentin, Karina Diniz Oliveira, Jose Luiz Costa
{"title":"High-sensitivity method for the determination of LSD and 2-oxo-3-hydroxy-LSD in oral fluid by liquid chromatography‒tandem mass spectrometry.","authors":"Kelly Francisco da Cunha, Julia Martinelli Magalhães Kahl, Taís Regina Fiorentin, Karina Diniz Oliveira, Jose Luiz Costa","doi":"10.1007/s11419-022-00622-0","DOIUrl":"https://doi.org/10.1007/s11419-022-00622-0","url":null,"abstract":"<p><strong>Purpose: </strong>We have developed and validated a high-sensitivity method to quantify lysergic acid diethylamide (LSD) and 2-oxo-3-hydroxy-LSD (OH-LSD) in oral fluid samples using liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC‒MS/MS). The method was applied to the quantification of both substances in 42 authentic oral fluid samples.</p><p><strong>Methods: </strong>A liquid-liquid extraction was performed using 500 µL each of samples (oral fluid samples collected using Quantisal™ device) and dichloromethane/isopropanol mixture (1:1, v/v). Enzymatic hydrolysis was evaluated to cleave glucuronide metabolites.</p><p><strong>Results: </strong>The limit of quantification was 0.01 ng/mL for both LSD and OH-LSD. The linearity was assessed between 0.01 and 5 ng/mL. Imprecision and bias were not higher than 10.2% for both analytes. Extraction recovery was higher than 69%. The analytes were stable in the autosampler at 10 °C for 24 h, and up to 30 days at 4 and -20 °C. The method was applied to the analysis of 42 oral fluid samples. LSD was detected in all samples (concentrations between 0.02 and 175 ng/mL), and OH-LSD was detected in 20 samples (concentrations between 0.01 and 1.53 ng/mL).</p><p><strong>Conclusions: </strong>A high-sensitive method was fully validated and applied to authentic samples. To our knowledge, this is the first work to report concentrations of LSD and OH-LSD in authentic oral fluid samples.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":"40 2","pages":"322-331"},"PeriodicalIF":2.2,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163268","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}