Drug Testing and Analysis最新文献

{"title":"Isolation and characterization of synthesis intermediates and side products in hexahydrocannabiphorol.","authors":"Willi Schirmer, Ilche Gjuroski, Martina Vermathen, Julien Furrer, Stefan Schürch, Wolfgang Weinmann","doi":"10.1002/dta.3759","DOIUrl":"https://doi.org/10.1002/dta.3759","url":null,"abstract":"<p><p>After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC-MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)-HHCP, iso-HHCP, cis-HHCP, and abn-HHCP) and two ketones (possible intermediates to (9R)-HHCP and abn-HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)-HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn-HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso-HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The analysis of methylamphetamine and para-hydroxy-methylamphetamine in post-mortem hair samples using liquid chromatography-tandem mass spectrometry.","authors":"Dylan Mantinieks, Olaf H Drummer, Jennifer Schumann, Dimitri Gerostamoulos","doi":"10.1002/dta.3765","DOIUrl":"https://doi.org/10.1002/dta.3765","url":null,"abstract":"<p><p>External contamination is a well-recognized limitation of hair analysis for drugs of abuse like methylamphetamine (MA), and there are no guidelines regarding the analysis of specific metabolites of MA to assist interpretation. We developed an analytical method to detect MA, amphetamine (AMP), and para-hydroxy-methylamphetamine (p-OH-MA) in hair and present their concentrations among a cohort of deceased persons positive for MA in blood (n = 63). Hair samples (≤ 3 cm) were washed with dichloromethane and water prior to extraction using a methanolic micro-pulverization. The reconstituted hair extracts were separated on a UCT Selectra® Aqueous C18 HPLC Column (100 × 2.1 mm, 3 μm) by gradient elution and detected using a Sciex Triple Quad 6500+ system. Validation was satisfactory, and the lower limits of quantitation were 0.01 ng/mg for MA and AMP and 0.001 ng/mg for p-OH-MA. The median hair concentrations of MA, AMP, and p-OH-MA were 13 ng/mg (range = 0.015-49; n = 51), 1.1 ng/mg (range = 0.018-44; n = 60), and 0.020 ng/mg (range = 0.0012-0.38, n = 62), respectively. These concentrations in hair were strongly positively correlated (r = .7202 to .8641, p < .001), suggesting similar modes of incorporation. Moreover, the wash/hair ratios were indicative of external contamination, especially among the soiled group of hair samples. Therefore, further studies are necessary to determine concentrations of p-OH-MA in living MA users and confirm if this metabolite constitutes a potential marker of MA consumption.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doping control of estra-4,9-diene-3,17-dione in horses.","authors":"Helen S M Ho, Adrian F Farrington, Amanda J Bond, Emmie N M Ho, Wing-Tak Wong","doi":"10.1002/dta.3756","DOIUrl":"https://doi.org/10.1002/dta.3756","url":null,"abstract":"<p><p>Estra-4,9-diene-3,17-dione (dienedione) is an anabolic-androgenic steroid (AAS) available on the market as a dietary supplement for bodybuilding. It is prohibited in both human and equine sports due to its potential performance-enhancing effect. With the rare presence of the 4,9-diene configuration in endogenous steroids, dienedione has been considered as a synthetic AAS. Nevertheless, the reoccurring detection of dienedione in entire male horse urine samples led to the investigation of its possible endogenous nature in horses, and its endogenous nature in entire male horses has been recently confirmed and reported by the authors' laboratory. While dienedione is not detected in castrated horses (geldings), it is essential to study its elimination and identify its metabolites for its effective control. To study the elimination and biotransformation of dienedione, administration experiments were performed by giving three castrated horses (geldings) each single oral dose of 1500 mg of dienedione powder for seven consecutive days. The postulated in vivo metabolites included 17-hydroxyestra-4,9-dien-3-one (M1a and M1b), hydroxylated dienedione (M2a, M2b, M3a, M3b, M4, M5) and hydroxylated M1 (M6a, M6b, M7a, M7b, M8a and M8b), formed from hydroxylation and reduction of dienedione. To control the misuse of dienedione in geldings, M3a and M3b are the potential targets that gave the longest detection time, which could be detected for up to 2-5 days in urine and 0.4-4 days in plasma.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dennis Hill.","authors":"","doi":"10.1002/dta.3757","DOIUrl":"https://doi.org/10.1002/dta.3757","url":null,"abstract":"","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doping control analysis of myo-inositol trispyrophosphate and 10 bisphosphonates in equine plasma by ion chromatography-mass spectrometry and its application to clodronic acid horse administration.","authors":"April Sum Yee Wong, Bruce Pui-Nam Yuen, Celia Oi Ling Wong, Fred Ka-Wai Kong, Yat-Ming So, Wai Him Kwok, Lydia Brooks, Terence See Ming Wan, Emmie Ngai-Man Ho","doi":"10.1002/dta.3753","DOIUrl":"https://doi.org/10.1002/dta.3753","url":null,"abstract":"<p><p>Bisphosphonates and myo-inositol trispyrophosphate (ITPP) are two classes of difficult-to-detect polar drugs that are prohibited under the rules of racing. ITPP is a drug capable of increasing the amount of oxygen in hypoxic tissues, and studies have shown that administration of ITPP increases the maximal exercise capacity in mice. The properties of ITPP make it an ideal candidate as a doping agent to enhance performance in racehorses. In recent years, ITPP had indeed been detected in racehorses and confiscated items. As for bisphosphonates, it is especially critical to control their use as since February 2019, the International Agreement on Breeding, Racing and Wagering (IABRW) by the International Federation of Horseracing Authorities (IFHA) had identified specific conditions on which bisphosphonates should not be administered to a racehorse. A recent review of literature shows that there is yet a simultaneous screening method for detecting ITPP and bisphosphonates in equine samples. This paper describes an efficient ion chromatography high-resolution mass spectrometry (IC-HRMS) method for the simultaneous detection of ITPP and 10 bisphosphonates at sub-parts-per-billion (ppb) to low-ppb levels in equine plasma after solid-phase extraction (SPE) and its application to an administration study of clodronic acid in horses.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute atrazine intoxication in heifers: Case report and toxicological studies.","authors":"Yolanda M Marron, Eduardo De Gerónimo, Juan I Poo, Juan A García, Gina Rustichelli Millán, Gastón E Britos, Fermín Lázaro, Germán J Cantón","doi":"10.1002/dta.3754","DOIUrl":"https://doi.org/10.1002/dta.3754","url":null,"abstract":"<p><p>Atrazine is a triazine organochloride herbicide, frequently used in different agricultural activities. Rare acute intoxication with atrazine is reported in production animals, and its metabolism in mammals is unknown. We report a spontaneous case of atrazine acute intoxication in 16.1% animals of a 168-beef heifer herd exposed to the herbicide at a farm located in Buenos Aires province, Argentina. Affected heifers showed different neurological signs and died suddenly, similar to the previous natural atrazine intoxication report. During autopsy, no gross lesions were observed. Different body fluids and tissues samples were collected during postmortem examination. No relevant histopathological findings were observed. High levels of atrazine and its metabolites were detected in different fluids and tissues by ultra-liquid chromatography high performance coupled to triple quadrupole mass spectrometry. These findings suggest ruminal or hepatic metabolization of atrazine in the exposed cattle. This is the first report of quantification and distribution of atrazine and its metabolites in intoxicated mammals providing relevant information for diagnostic purposes.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and analytical characterization of 1-(2-thienoyl)-6-allyl-nor-d-lysergic acid diethylamide (1T-AL-LAD).","authors":"Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Kenji Tsujikawa, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1002/dta.3747","DOIUrl":"https://doi.org/10.1002/dta.3747","url":null,"abstract":"<p><p>Lysergic acid diethylamide (LSD) analogs have emerged as new psychoactive substances (NPS) since the mid-2010s, and new compounds continue to emerge for recreational use. Since the end of 2023, \"1D-AL-LAD\" appeared on X (formerly Twitter) and other websites. As for the compound \"1D-LSD\" (which also has \"1D\" in the name), several studies show that the ingredient of seized blotter paper printed \"1D-LSD\" was actually 1-(2-thienoyl)-LSD (1T-LSD). However, there are no reports of seizures of 1-(1,2-dimethylcyclobutanecarbonyl)-LSD (1D-LSD). Accordingly, it was considered that all or at least a certain percentage of \"1D-AL-LAD (1-(1,2-dimethylcyclobutanecarbonyl)-6-allyl-nor-LSD)\" is actually 1-(2-thienoyl)-6-allyl-nor-LSD (1T-AL-LAD). This compound is handled by a number of distributors as of April 2024; therefore, it should be characterized in advance if seized. In this study, 1T-AL-LAD was synthesized and characterized using nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, liquid chromatography/high-resolution mass spectrometry (LC/HRMS) and gas chromatography/MS (GC/MS). This compound was easily distinguished from previously reported lysergamides. There were some differences in the detectability of 1T-AL-LAD compared with other lysergamides using GC/MS and the fragmentation patterns in LC/HRMS. These differences can be reasonably explained. This information will be of help to determine this substance in seized materials should it emerge on the market.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro activation of the CB₁ receptor by the semi-synthetic cannabinoids hexahydrocannabinol (HHC), hexahydrocannabinol acetate (HHC-O) and hexahydrocannabiphorol (HHC-P).","authors":"Mattias Persson, Robert Kronstrand, Michael Evans-Brown, Henrik Green","doi":"10.1002/dta.3750","DOIUrl":"https://doi.org/10.1002/dta.3750","url":null,"abstract":"<p><p>Semi-synthetic cannabinoids (SSCs) including hexahydrocannabinol (HHC) are emerging on the drug market and sold openly as purportedly legal replacements for cannabis and Δ⁹-THC. By the beginning of 2024, 24 European countries had identified HHC, often sold openly in edibles (foods/candy), vapes and low-THC cannabis flowers and resins. The SSC market is developing rapidly, with HHC acetate (HHC-O), hexahydrocannabiphorol (HHC-P) and others recently identified. These developments may mark the first major change in the market for 'legal' replacements to cannabis since 'Spice' containing synthetic cannabinoids, such as JWH-018, emerged in 2008. Currently, there are some data available on the pharmacology of SSCs, which is crucial for understanding their effects, evaluating health risks and informing public health responses. This study focused on characterizing the in vitro activation of the human CB₁ receptor by the (R)- and (S)-epimers of HHC, HHC-P and HHC-O. Using recombinant CHO-K1 cells expressing the human CB₁ receptor, the potency (EC₅₀) and efficacy were determined. It was established that (9R)-HHC and (9R)-HHC-P activated the CB₁ receptor as partial agonists and with five and two times lower potency compared to JWH-018, respectively, while the (S)-epimers exhibited even lower potency. The (R)-epimer of HHC-O activate the CB₁ receptor to even lesser extent and the (S)-epimer showed no activation. For HHC and HHC-P, all epimers exhibited similar level of efficacy. This available evidence suggests cannabimimetic effects of the tested SSC with the exception for the acetates that likely function as pro-drugs in vivo.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confirmation of ethanol administration in racing greyhounds by LC-MS-MS.","authors":"Adam Cawley, Steven Karamatic, Gordon Sutton, D Brynn Hibbert, Andrew R McKinney, Samantha Nelis, Karen Caldwell, E Bruce Young, Stacey Richards, John Keledjian","doi":"10.1002/dta.3751","DOIUrl":"https://doi.org/10.1002/dta.3751","url":null,"abstract":"<p><p>Ethanol is a prohibited substance in professional animal racing as its administration causes physiological effects such as depression of the central nervous system. Regulation of potential doping agents, including those that inhibit performance, is critical to ensure integrity and animal welfare in greyhound racing, but the detection of ethanol is complicated by dietary and/or environmental exposure. In response, a reliable analytical method capable of detecting recent ethanol administration in greyhound urine samples was validated and implemented. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) was used to investigate the variation in urinary ethanol metabolites; ethyl-β-D glucuronide (EG; <math> <semantics> <mrow> <msub><mover><mi>γ</mi> <mo>¯</mo></mover> <mi>EG</mi></msub> </mrow> <annotation>$$ {overline{gamma}}_{mathrm{EG}} $$</annotation></semantics> </math>  = 1.0 μg/ml, <math> <semantics> <mrow><msub><mi>s</mi> <mi>EG</mi></msub> </mrow> <annotation>$$ {s}_{mathrm{EG}} $$</annotation></semantics> </math>  = 3.3 μg/ml) and ethyl sulfate (ES; <math> <semantics> <mrow> <msub><mover><mi>γ</mi> <mo>¯</mo></mover> <mi>ES</mi></msub> </mrow> <annotation>$$ {overline{gamma}}_{mathrm{ES}} $$</annotation></semantics> </math>  = 0.9 μg/ml, <math> <semantics> <mrow><msub><mi>s</mi> <mi>ES</mi></msub> </mrow> <annotation>$$ {s}_{mathrm{ES}} $$</annotation></semantics> </math>  = 1.9 μg/ml) levels from a reference population of 202 racing greyhounds. These were compared to urine samples collected following administration of ethanol to one male and one female greyhound. Results were used to establish a threshold within the national rules of greyhound racing: <math> <semantics> <mrow> <msub><mover><mi>γ</mi> <mo>¯</mo></mover> <mi>EG</mi></msub> </mrow> <annotation>$$ {overline{gamma}}_{mathrm{EG}} $$</annotation></semantics> </math> and <math> <semantics> <mrow> <msub><mover><mi>γ</mi> <mo>¯</mo></mover> <mi>ES</mi></msub> </mrow> <annotation>$$ {overline{gamma}}_{mathrm{ES}} $$</annotation></semantics> </math>  > 20 μg/ml in urine are defensible criteria to confirm ethanol administration to greyhounds. Case studies of competition samples are provided to demonstrate the forensic translation of this work.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The undetected murder? Evaluation and validation of a practicable and rapid inductively coupled plasma-mass spectrometry method for the detection of arsenic, lead, and thallium intoxications in postmortem blood.","authors":"Martin H J Wiesen, Dennis Schneider, Wolfgang Hein, Thomas Streichert, Martin Jübner, Hilke Andresen-Streichert","doi":"10.1002/dta.3749","DOIUrl":"https://doi.org/10.1002/dta.3749","url":null,"abstract":"<p><p>Homicide, suicide, or accident - elemental intoxication may be a cause in each of these types of deaths. Inductively coupled plasma mass spectrometry (ICP-MS) has emerged as the gold standard analytical method for toxic metal analysis in both clinical and forensic settings. An ICP-MS method was developed using a modified acidic workup for the quantitative determination of arsenic, lead, and thallium. Method validation focused on the assessment of linearity, between- and within-day precisions, limits of detection (LoD) and lower limits of quantification (LLoQ), and carryover. The method was applied to analysis of postmortem peripheral blood samples from 279 forensic cases for which orders for chemical-toxicological examination had been received from the public prosecutor's office. Using six-point and one-point calibrations (latter for rapid screening purposes), precisions and accuracies ranged from -4.8 to 5.8% and -6.4 to 7.5%. Analytical sensitivities for As, Pb, and Tl were 0.08, 0.18, and 0.01 μg/l (LoD) and 0.23, 0.66, and 0.03 μg/l (LLoQ), respectively. Observed postmortem peripheral blood concentrations were As, 1.31 ± 3.42 μg/L; Pb, 17.4 ± 13.1 μg/L; and Tl, 0.11 ± 0.07 μg/L (mean ± standard deviation [SD]). Elemental concentrations, determined in additional quality control samples, were in good agreement to those obtained with an external ICP-MS method based on alkaline sample processing. The current method is practicable and compatible with an ICP-MS system used for trace element analysis in an accredited medical laboratory. It allows for implementation of low-threshold investigations when metal intoxications are suspected in forensic routine.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}