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An NMR study on the keto-enol tautomerism of 1,3-dicarbonyl drug precursors. 关于 1,3-二羰基药物前体的酮烯醇同分异构体的核磁共振研究。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-17 DOI: 10.1002/dta.3789
Xue-Yan Liu, Wei Jia, Cui-Mei Liu, Zhen-Dong Hua
{"title":"An NMR study on the keto-enol tautomerism of 1,3-dicarbonyl drug precursors.","authors":"Xue-Yan Liu, Wei Jia, Cui-Mei Liu, Zhen-Dong Hua","doi":"10.1002/dta.3789","DOIUrl":"https://doi.org/10.1002/dta.3789","url":null,"abstract":"<p><p>The effective implementation of drug precursor legislation has driven the innovation and design of new alternative substances. The application of 1,3-dicarbonyl precursors as alternative precursors for the synthesis of 1-phenyl-2-propanone (P2P) and 3,4-methylenedioxyphenyl-2-propanone (MDP2P) has created new challenges to legal control. Their 1,3-dicarbonyl structure allows the precursors to exist as an equilibrium mixture of the tautomeric diketo and keto-enolic forms during the nuclear magnetic resonance (NMR) analysis. In this study, the keto-enol tautomerism of four 1,3-dicarbonyl drug pre-precursors, α-phenylacetoacetamide (APAA), methyl α-phenylacetoacetate (MAPA), ethyl α-phenylacetoacetate (EAPA), and methyl 2-(benzo[d][1,3]dioxol-5-yl)-3-oxobutanoate (MAMDPA) were investigated through NMR. One-dimensional (1D) and 2D NMR were combined to assign signals for the diketo and keto-enolic tautomers. Results showed that the keto-enol tautomerism was solvent-dependent but was also influenced by the substituent present in the molecule. Further, the analysis results indicated that majority of substances existed mainly in the diketo form. The enol-keto equilibrium constant (K<sub>eq</sub>) was stable in dimethyl sulfoxide-d<sub>6</sub> and chloroform-d, while unstable for some compounds in acetone-d<sub>6</sub> and deuterated methanol. The presence of impurities in the seized sample may disrupt the equilibrium between keto-enol tautomers in 1,3-dicarbonyl precursors. After the optimization of several key quantitative parameters, a quantitative NMR method for the quantification of 1,3-dicarbonyl drug precursors were also developed to facilitate their quantitative analysis. This is the first study to investigate the keto-enol tautomerism and quantification of 1,3-dicarbonyl drug precursors by NMR, providing a new approach for structure analysis and quantification of new precursor analogues.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994844","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}
引用次数: 0
Beta2-adrenergic agonist salbutamol exhibits enantioselective disposition in skeletal muscle of lean young men following oral administration. β2-肾上腺素能受体激动剂沙丁胺醇口服后在精瘦年轻男性骨骼肌中呈现对映体选择性处置。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-16 DOI: 10.1002/dta.3787
Morten Hostrup, Glenn A Jacobson, Kasper Eibye, Christian K Narkowicz, David S Nichols, Søren Jessen
{"title":"Beta<sub>2</sub>-adrenergic agonist salbutamol exhibits enantioselective disposition in skeletal muscle of lean young men following oral administration.","authors":"Morten Hostrup, Glenn A Jacobson, Kasper Eibye, Christian K Narkowicz, David S Nichols, Søren Jessen","doi":"10.1002/dta.3787","DOIUrl":"https://doi.org/10.1002/dta.3787","url":null,"abstract":"<p><p>Salbutamol is a common short-acting beta<sub>2</sub>-adrenergic agonist used in treatment of asthma and exercise-induced bronchoconstriction but also possesses anabolic and metabolic actions in skeletal muscle. As a chiral compound, salbutamol is a racemic 1:1 mixture of two enantiomers, (R)-salbutamol and (S)-salbutamol, which exhibit divergent pharmacokinetic and pharmacodynamic actions. Despite salbutamol being available for decades, information on the enantioselective disposition of salbutamol enantiomers in human skeletal muscle is absent. In this study, we determined concentrations of (R)-salbutamol and (S)-salbutamol by UHPLC-MS/MS in arterial plasma and vastus lateralis muscle samples from 12 lean young men 2½ and 7 h following ingestion of 24 mg oral salbutamol. Mean (range) arterial plasma concentrations were 10-fold higher (p < 0.001) for (S)-salbutamol than (R)-salbutamol, being 33(9-62) and 49(30-84) ng·mL<sup>-1</sup> for (S)-salbutamol and 4 (1-6) and 4 (2-5) ng·mL<sup>-1</sup> for (R)-salbutamol 2½ and 7 h following administration, respectively, reflecting faster elimination of the (R)-enantiomer. Mean (range) muscle concentrations were higher (p < 0.001) for (S)-salbutamol than (R)-salbutamol 2½ h (0.17 [0.1-0.26] vs. 0.04 [0.02-0.06]) and 7 h (0.31 [0.21-0.46] vs. 0.06 [0.04-0.12] ng·mg<sub>d.w.</sub> <sup>-1</sup>) after administration. However, muscle:plasma partition coefficient was two-fold higher (p < 0.001) for (R)-salbutamol than (S)-salbutamol 7 h following administration. These observations demonstrate that oral salbutamol exhibits enantioselective disposition in systemic circulation and muscle favoring the (S)-enantiomer but with higher relative partitioning of the (R)-enantiomer in skeletal muscle. Furthermore, the concentration-time profiles of salbutamol enantiomers are different in skeletal muscle and systemic circulation following oral ingestion. These findings have implications for the application of chiral switch (R)-salbutamol in doping control.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986987","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}
引用次数: 0
Interlaboratory comparison of phosphatidylethanol in dried blood spots using different sampling devices. 使用不同采样装置对干血斑中磷脂酰乙醇含量进行实验室间比较。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-16 DOI: 10.1002/dta.3784
Matthias Bantle, Frederike Stöth, Wolfgang Weinmann, Marc Luginbühl
{"title":"Interlaboratory comparison of phosphatidylethanol in dried blood spots using different sampling devices.","authors":"Matthias Bantle, Frederike Stöth, Wolfgang Weinmann, Marc Luginbühl","doi":"10.1002/dta.3784","DOIUrl":"https://doi.org/10.1002/dta.3784","url":null,"abstract":"<p><p>Phosphatidylethanol (PEth) has become an important marker to assess drinking behaviour and monitor abstinence. Despite its increasing use, knowledge on robustness and standardization and comparability of methods and results are still limited. In 2022, the first international consensus for the use of PEth and its interpretation was published. To establish an experience-based foundation for further harmonization, three rounds of interlaboratory comparison using microsamples were conducted. Participating laboratories sent their sampling devices to the laboratory of Forensic Toxicology at the University of Bern, where for each round, four different authentic blood samples were applied to the devices and sent back. The PEth 16:0/18:1 target concentrations covered a range between 16 and 474 ng/mL (0.023 and 0.676 μmol/L, respectively) and included sample concentrations close to the decision limits of 20 and 200 ng/mL (0.025 and 0.28 μmol/L, respectively). Evaluation of the results based on guidelines by Horwitz and the Society of Toxicological and Forensic Chemistry (GTFCh) showed that 73% of all participating laboratories quantified and reported all samples (N = 4 for each round) within the acceptable limits. More than 90% quantified and reported at least one sample within the acceptable limits.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986988","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}
引用次数: 0
Quantitative analysis of nonsteroidal anti-inflammatory drugs in dried blood spot from mountain ultra-trail runners. Contribution of pharmacokinetic models for the interpretation of the results. 山地越野跑者干血斑中非甾体抗炎药物的定量分析。药代动力学模型对解读结果的贡献。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-15 DOI: 10.1002/dta.3781
Mohammad Shafiq Mashal, Jérôme Guitton, Pierre Sallet, Laurent Bourguignon, Christelle Machon
{"title":"Quantitative analysis of nonsteroidal anti-inflammatory drugs in dried blood spot from mountain ultra-trail runners. Contribution of pharmacokinetic models for the interpretation of the results.","authors":"Mohammad Shafiq Mashal, Jérôme Guitton, Pierre Sallet, Laurent Bourguignon, Christelle Machon","doi":"10.1002/dta.3781","DOIUrl":"https://doi.org/10.1002/dta.3781","url":null,"abstract":"<p><p>Monitoring of drug use in athletes is of interest both for health and competition-related issues. Considering the advantages of Dried Blood Sampling (low invasiveness, easy sampling, long term storage), we have validated a quantitative LC-MS/HRMS method for the screening of 16 nonsteroidal anti-inflammatory drugs. For all drugs, accuracy and imprecision were within 15% for the 3 levels of quality control and lower than 20% for the lower limit of quantification. Application was performed from samples obtained for Ultra-Trail du Mont-Blanc® 2021 and 2022. A focus on ibuprofen and its metabolites (hydroxyibuprofen, carboxyibuprofen, ibuprofen glucuronide and hydroxyibuprofen glucuronide) was made because the results showed that it was the most detected nonsteroidal anti-inflammatory drug. Further, an interpretation of the ibuprofen concentrations was proposed either from experimental data obtained after an intake of ibuprofen by 10 control subjects, or from a pharmacokinetic modelling and simulations. Depending on the analytical performances of the method, we proposed possible detection windows for ibuprofen in runners. The pharmacokinetic model made it possible to consider two scenarios with and without modification of the total clearance of ibuprofen linked to a modification of the pharmacokinetics of the drugs due to the practice of a long and intense physical activity.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986989","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}
引用次数: 0
Identification of human metabolites of fast skeletal troponin activators Tirasemtiv and Reldesemtiv for doping control purposes. 为兴奋剂控制目的鉴定快速骨骼肌钙蛋白激活剂 Tirasemtiv 和 Reldesemtiv 的人体代谢物。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-13 DOI: 10.1002/dta.3786
Luisa Euler, Kim Deinert, Felicitas Wagener, Katja Walpurgis, Mario Thevis
{"title":"Identification of human metabolites of fast skeletal troponin activators Tirasemtiv and Reldesemtiv for doping control purposes.","authors":"Luisa Euler, Kim Deinert, Felicitas Wagener, Katja Walpurgis, Mario Thevis","doi":"10.1002/dta.3786","DOIUrl":"https://doi.org/10.1002/dta.3786","url":null,"abstract":"<p><p>The fast skeletal troponin activators (FSTAs) Reldesemtiv and Tirasemtiv were developed for patients suffering from neuro-degenerative diseases of the motor nervous system, e.g. amyotrophic lateral sclerosis (ALS). The drug candidates can increase the sensitivity of troponin C to calcium by selectively activating the troponin complex resulting in increased skeletal muscle contraction. Although the development of the drug candidates is currently discontinued because of missed end points in phase III clinical studies with patients with ALS, phase I clinical trials showed an increase in muscle contraction force in healthy humans. This effect could be abused by athletes to enhance performance in sports. As the substances are listed on the 2024 edition of the World Anti-Doping Agency's Prohibited List, the aim of this study was to identify and characterize metabolites of Reldesemtiv and Tirasemtiv to ensure their reliable identification in doping control analyses. The biotransformation of the drug candidates was studied in vitro using pooled human liver microsomes and 3D cultivated human hepatic cells of the cell line HepaRG, yielding a total of 11 metabolites of Reldesemtiv and eight of Tirasemtiv. In addition, a human elimination study was conducted to investigate the metabolism and elimination profile of Tirasemtiv and Reldesemtiv in vivo, suggesting the N-glucuronide of Tirasemtiv and hydroxylated 3-fluoro-2-(3-fluoro-1-methylcyclobutyl)pyridine as well as its glucuronide as suitable target analytes for routine doping controls. Applying a validating HPLC-MS/MS method, optimized to detect Reldesemtiv and Tirasemtiv in human urine, microdosing (50 μg) of each substance was traceable for 24-72 h.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974631","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}
引用次数: 0
In vivo comparative study of hemp straw exposure and cannabidiol oil administration in horse urine. 马尿中大麻秸秆暴露与大麻二酚油给药的体内比较研究。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-08 DOI: 10.1002/dta.3783
Stéphane Trevisiol, Marie-Agnès Popot, Patrice Garcia, Sophie Boyer, Mylène Caroff, Laura Drif, Wafek Taleb, Sophie Tendon, Yves Moulard, Ludovic Bailly-Chouriberry
{"title":"In vivo comparative study of hemp straw exposure and cannabidiol oil administration in horse urine.","authors":"Stéphane Trevisiol, Marie-Agnès Popot, Patrice Garcia, Sophie Boyer, Mylène Caroff, Laura Drif, Wafek Taleb, Sophie Tendon, Yves Moulard, Ludovic Bailly-Chouriberry","doi":"10.1002/dta.3783","DOIUrl":"https://doi.org/10.1002/dta.3783","url":null,"abstract":"<p><p>The non-psychoactive cannabinoids cannabidiol (CBD) and cannabidiolic acid (CBDA) are available on the market in different forms, mostly for their anti-inflammatory and potential analgesic properties. These substances are prohibited during equine competitions. CBD and CBDA are naturally present in hemp straw, commonly used as a bedding substitute for wheat straw. Unfortunately, horses can eat it, which therefore could lead to a possible risk of positive findings for CBD/CBDA in biological samples after doping control tests. The goals of this study were, first, to provide recommendations on the use of hemp straw before competition and, second, to assess if discrimination between hemp bedding exposure and CBD oil administration is possible. Several CBD equine in vivo studies have been conducted, including one on hemp straw used as bedding and one after administration of CBD oil by topical and sublingual routes. In hemp straw, CBDA was detected in higher quantities than CBD, and other cannabinoids have been observed. After hemp straw exposure, CBDA was also detected in higher quantities than CBD in all urine samples. It appeared that hemp straw should not be used as bedding for equine competition except if a delay of at least 48 h is respected. Regarding the CBD oil product analysis, CBD was the main compound detected. After administration, 7-hydroxy CBD was identified in the urine. In conclusion, based on these data, we highlighted that it could be possible to discriminate the exposure of a horse to hemp straw from an administration of a CBD oil product thanks to the main presence of CBDA.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905241","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}
引用次数: 0
Evaluation of spectroscopic techniques for on-site drug testing of festival seizures. 评估用于对节日发作进行现场药物检测的光谱技术。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-05 DOI: 10.1002/dta.3780
N Meert, J Eliaerts, F Van Durme, S M R Wille, N Samyn
{"title":"Evaluation of spectroscopic techniques for on-site drug testing of festival seizures.","authors":"N Meert, J Eliaerts, F Van Durme, S M R Wille, N Samyn","doi":"10.1002/dta.3780","DOIUrl":"https://doi.org/10.1002/dta.3780","url":null,"abstract":"<p><p>Despite the fact that drugs of abuse are illegal, a drug-free festival still remains an utopia in most settings. For law enforcement purposes, it is necessary to rapidly determine whether controlled substances are involved. On-site testing is a challenging task because drugs appear in different physical forms and concentrations. The aim of this study was to compare the performance of two spectroscopic techniques, Raman and Fourier transform-infrared (FT-IR), for the testing of drug seizures at a dance festival. First, samples were measured through packaging with Raman. Subsequently, homogenized samples were analysed with FT-IR. For MDMA tablets, a chemometric model was applied on the FT-IR spectra for the dose estimation. After the festival, results were confirmed in the forensic laboratory with gas chromatography coupled with mass spectrometry (GC-MS) and gas chromatography with flame ionization detection (GC-FID). In total, 166 samples of which 90 tablets, 53 powders, 16 crystals and 7 liquids were analysed. MDMA, cocaine and ketamine were the top three drugs seized. The Raman technique was suitable for powders and crystals (sensitivity of 100% and 81%, respectively). However, in comparison with FT-IR, Raman performance was lower for the analysis of liquids (sensitivity of 67%) and 'ecstasy'-like tablets (sensitivity of 41%). Overall, sensitivities above 95% were obtained with FT-IR. The MDMA doses of the tablets, determined on-site, ranged between 52 mg and 336 mg MDMA hydrochloride. For a quick identification of a variety of drugs on-site, the combination of Raman and FT-IR is recommended. It should be emphasized that optimized settings, in-house libraries and analysis by trained operators are essential to obtain correct results.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892452","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}
引用次数: 0
Enhanced analysis of equine plasma for the presence of recombinant human erythropoietin - Implementation of an improved workflow. 马血浆中重组人促红细胞生成素的强化分析 - 改进工作流程的实施。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-04 DOI: 10.1002/dta.3785
Stacey Richards, David Palmer, Adam Cawley, Martin Wainscott, John Keledjian
{"title":"Enhanced analysis of equine plasma for the presence of recombinant human erythropoietin - Implementation of an improved workflow.","authors":"Stacey Richards, David Palmer, Adam Cawley, Martin Wainscott, John Keledjian","doi":"10.1002/dta.3785","DOIUrl":"https://doi.org/10.1002/dta.3785","url":null,"abstract":"<p><p>An improved screening workflow and a robust capillary flow LC-MS confirmatory method for the detection of recombinant human erythropoietin (rHuEPO) has been implemented to increase the sensitivity of rHuEPO detection and to reduce the number of suspect samples committed to confirmatory testing. The influence of repeated dosing of epoetin-β on the detection window of rHuEPO in equine plasma was assessed using the optimised method. Samples were initially assessed using an economical R&D Human EPO Duo-Set ELISA Development System. Samples indicating a result greater than the batch baseline were analysed using the complementary R&D Human EPO Quantikine IVD ELISA kit. All samples recording an abnormal screening result were subjected to confirmatory analysis. Confirmation of rHuEPO in plasma (≥2.5 ml) in the range of 4-13 mIU/ml (n = 6) was achieved using immunoaffinity enrichment, tryptic digestion, and capillary flow LC-MS/MS. Four horses were administered a single dose of epoetin-β (10,000 IU) via the subcutaneous and intravenous routes, on two occasions, seven days apart. The excretion profile was rapid with epoetin-β detection times of 48 to 72 h following each administration, with no appreciable difference observed between the two routes of administration. This workflow has been shown as an effective anti-doping strategy related to rHuEPO misuse and supports the use of out-of-competition testing of horses in the 2 to 3-day period prior to race-day.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887761","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}
引用次数: 0
Interest of hair tests to discriminate a tail end of a doping regimen from a possible contamination in case of challenging an anti-doping rule violation. V. Case reports involving trimetazidine, a drug where the concentration after a single 20 mg dose has been established. 在对违反反兴奋剂规则的行为提出质疑时,利用毛发检测来鉴别使用兴奋剂疗程的 尾期和可能存在的污染。V. 涉及曲美他嗪的案例报告,这种药物单次服用 20 毫克后的浓度已经确定。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-01 DOI: 10.1002/dta.3775
Pascal Kintz, Alice Ameline, Laurie Gheddar
{"title":"Interest of hair tests to discriminate a tail end of a doping regimen from a possible contamination in case of challenging an anti-doping rule violation. V. Case reports involving trimetazidine, a drug where the concentration after a single 20 mg dose has been established.","authors":"Pascal Kintz, Alice Ameline, Laurie Gheddar","doi":"10.1002/dta.3775","DOIUrl":"https://doi.org/10.1002/dta.3775","url":null,"abstract":"<p><p>The identification of trimetazidine, a medicine used for treating stable angina pectoris and for preventing angina attacks, has been recently observed in doping cases involving high profile athletes from various countries over the world. In all the files where the authors have been involved, the urine concentration of trimetazidine was low (<2 ng/mL), and the athletes argued that contamination was the source of their adverse analytical finding. It is possible to challenge imposed sanctions in relation to an adverse analytical finding, but it is the responsibility of the athlete to demonstrate he/she is innocent and can qualify for no fault or negligence. When the delay between the urine collection and the notification of the violation was not too long (less than 6 months), these athletes requested a head hair test. Trimetazidine was analyzed by an original LC-MS/MS method involving pH 9.5 borate buffer overnight incubation of 20 mg and subsequent solvents extraction in presence of trimetazidine-D8 used as internal standard. Linearity was verified from 1 to 200 pg/mg (R<sup>2</sup> = 0.9987). Limit of detection of the method was 0.1 pg/mg. The hair specimen of a male subject, collected 4 weeks after single oral ingestion of 20 mg trimetazidine, tested positive at 146 pg/mg in the corresponding segment. Concentrations of trimetazidine measured in several hair specimens (n = 5) collected from athletes challenging their anti-doping rule violation were below 1 pg/mg, which is consistent with incidental exposure due to contamination. This is the first evidence that trimetazidine is incorporated in human hair after a single therapeutic dose administration.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858351","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}
引用次数: 0
Determination of amphetamines in hair samples using microextraction by packed sorbent and gas chromatography-mass spectrometry. 利用填料吸附剂微萃取和气相色谱-质谱法测定毛发样本中的苯丙胺。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-07-31 DOI: 10.1002/dta.3779
Bruno Pires, Ana Y Simão, Tiago Rosado, Mário Barroso, Eugenia Gallardo
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