Drug Testing and Analysis最新文献

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Evaluation of Minimum Reporting Limits to Determine In-Competition Use of Stimulants. 对确定赛内使用兴奋剂的最低报告限值进行评估。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-09-15 DOI: 10.1002/dta.3799
Vinod S Nair, Fatjon A Hanelli, Chad Moore, Jenna M Goodrum, Geoffrey D Miller, Andre Crouch, Daniel Eichner
{"title":"Evaluation of Minimum Reporting Limits to Determine In-Competition Use of Stimulants.","authors":"Vinod S Nair, Fatjon A Hanelli, Chad Moore, Jenna M Goodrum, Geoffrey D Miller, Andre Crouch, Daniel Eichner","doi":"10.1002/dta.3799","DOIUrl":"https://doi.org/10.1002/dta.3799","url":null,"abstract":"<p><p>The applicability of urinary minimum reporting limits (MRLs) to determine in-competition use of prohibited substances is an evolving topic. Most stimulants are subject to a universal MRL, despite the wide range of commercially available dosages for commonly used stimulants. Further, it is unknown whether the urinary MRL is reflective of a pharmacological dose ingested after the start of the in-competition period. To evaluate whether urinary MRLs can distinguish between in-competition and out-of-competition use, a controlled administration study was performed with three commonly used stimulants-amphetamine, methylphenidate, and modafinil at relatively low but therapeutically relevant dosages. Four to six volunteers were administered a particular drug once per day for five consecutive days. Urine, serum, dried blood spots (DBS), and oral fluid (OF) were collected during the active administration period and for 48 h after cessation of use. For all participants, urinary concentrations for all target analytes exceeded the MRL even 48 h after cessation of use. In serum and DBS, most volunteers showed detectable amounts at 48 h post use. Peak concentrations were variable between target compounds even with similar administered dosages. Further, there was a reproducible difference between serum and DBS concentrations. Interpretation of results from OF measurements was challenging due to the inability to normalize for hydration status and OF viscosity. Analyte concentrations decreased steadily over the washout period but did not correlate across matrices for all target analytes. The study reiterates the challenges associated with determining in-competition use by relying on urinary concentrations.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277610","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
Pharmacokinetics of Ethyl Glucuronide and Ethyl Sulfate and Pharmacodynamic Effects Following Intravenous and Oral Administration of Ethanol to Exercised Horses. 给运动马静脉注射和口服乙醇后,乙醇葡萄糖醛酸乙酯和硫酸乙酯的药代动力学及药效学效应。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-09-15 DOI: 10.1002/dta.3803
Heather K Knych, Jeff Blea, Mary Scollay, Philip H Kass, Daniel S McKemie
{"title":"Pharmacokinetics of Ethyl Glucuronide and Ethyl Sulfate and Pharmacodynamic Effects Following Intravenous and Oral Administration of Ethanol to Exercised Horses.","authors":"Heather K Knych, Jeff Blea, Mary Scollay, Philip H Kass, Daniel S McKemie","doi":"10.1002/dta.3803","DOIUrl":"https://doi.org/10.1002/dta.3803","url":null,"abstract":"<p><p>Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to \"calm a horse's nerves.\" In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at various times post administration for up to 24 h. Concentrations of ethyl glucuronide and ethyl sulfate were determined using liquid chromatography-tandem mass spectrometry and pharmacokinetic analysis performed. Behavioral, locomotor activity and effects on heart rate were assessed. The maximum concentration (mean ± SD) of ethyl glucuronide was 71.5 ± 42.7 and 105.0 ± 47.5 ng/mL at 0.88 h following IV and oral administration, respectively. The maximum concentrations for the ethyl sulfate metabolite following IV and oral administration were 1.61 ± 0.60 and 3.46 ± 1.68 ng/mL, respectively. Urine concentrations of both metabolites were non-detectable by 24 h post ethyl alcohol administration. No observable behavioral responses were noted following IV or oral administration. Significant decreases in heart rate were noted at various times starting at 10 min until 4 h post administration in the oral dose group. Both ethyl glucuronide and ethyl sulfate could be useful markers for detection of illicit administration of ethanol to horses.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277630","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
Rapid Analytical Method for Quantification of Gamma-Hydroxybutyrate (GHB) in Hair by UPLC-MS/MS. 利用 UPLC-MS/MS 快速分析方法定量毛发中的γ-羟丁酸(GHB)。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-09-15 DOI: 10.1002/dta.3798
Miriam Blanco-Ces, Ana de-Castro-Rios, Angela Lopez-Rabuñal, Maria Cobo-Golpe, Angelines Cruz, Elena Lendoiro
{"title":"Rapid Analytical Method for Quantification of Gamma-Hydroxybutyrate (GHB) in Hair by UPLC-MS/MS.","authors":"Miriam Blanco-Ces, Ana de-Castro-Rios, Angela Lopez-Rabuñal, Maria Cobo-Golpe, Angelines Cruz, Elena Lendoiro","doi":"10.1002/dta.3798","DOIUrl":"https://doi.org/10.1002/dta.3798","url":null,"abstract":"<p><p>Gamma-hydroxybutyrate (GHB), an endogenous compound related to the neurotransmitter gamma-aminobutyric acid (GABA), is used as a therapeutic and recreational drug and as a \"weapon\" in drug-facilitated crimes. The very short window of detection of GHB in conventional matrices (blood and urine) makes necessary the use of alternative matrices like hair. Hair has a long window of detection and the possibility to perform segmental analysis, which makes it very useful for proving GHB intake. In the present work, a method for quantification of GHB in hair was developed and validated. Hair (10 mg) was washed twice with dichloromethane and then incubated at room temperature with Milli-Q water in an ultrasound bath for 30 min. Analysis was performed by UPLC-MS/MS using a CORTECS UPLC HILIC (1.6 μm), 2.1 × 100-mm column, and a gradient with acetonitrile and ammonium acetate (10 mM) at pH 6.0, with a total run-time of 10 min. For detection, a triple quadrupole mass spectrometer in ESI negative mode was used. The method was validated, following the criteria established in the \"AAFS Standard Practices for Method Validation in Forensic Toxicology\" guideline, obtaining satisfactory results for linearity (0.5-50 ng/mg), accuracy (95.0%-103.2%), imprecision (< 10.2%), limit of detection (0.1 ng/mg) and quantification (0.5 ng/mg), exogenous selectivity (no interferences), matrix effect (less than -44.2%), extraction efficiency (> 86.4%), process efficiency (> 46.1%), and autosampler stability (< 4.3%). The method was used for the analysis of 26 authentic hair samples, 25 from non-drug users, obtaining values between < LOQ and 6.25 ng/mg of endogenous GHB and 1 from a former GHB chronic user to prove abstinence.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277632","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
Step-By-Step Procedure to Identify Previously Unknown Compounds by LC-QTOF-MS Exemplified by an Intoxication With the Methaqualone Analog SL-164. 通过 LC-QTOF-MS 鉴别以前未知化合物的分步程序,以使用甲喹酮类似物 SL-164 的中毒事件为例。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-09-04 DOI: 10.1002/dta.3792
Helena Fels, Simon Franz, Torsten Dame, Gisela Skopp, Frank Musshoff
{"title":"Step-By-Step Procedure to Identify Previously Unknown Compounds by LC-QTOF-MS Exemplified by an Intoxication With the Methaqualone Analog SL-164.","authors":"Helena Fels, Simon Franz, Torsten Dame, Gisela Skopp, Frank Musshoff","doi":"10.1002/dta.3792","DOIUrl":"https://doi.org/10.1002/dta.3792","url":null,"abstract":"<p><p>In September 2019, a 22-year-old man with a history of drug abuse presented to the hospital with altered mental status. Due to a suspected drug overdose, a blood sample taken on admission and a urine sample collected 30 h thereafter were submitted to our laboratory to test for illegal drugs, pharmaceutical substances, and designer drugs. During the routine toxicological analysis of the serum sample, morphine and phenobarbital were identified by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Additionally, two compounds showing identical accurate masses and isotope ratios as the designer benzodiazepine diclazepam and the benzodiazepine lormetazepam were found. However, retention times differed significantly from the expected values, and the acquired MS/MS spectra did not match the library entries of the two compounds, indicating the presence of two previously unknown substances. After further investigation, SL-164 (5-chloro-3-(4-chloro-2-methylphenyl)-2-methyl-4(3H)-quinazolinone), a methaqualone analog, which has recently emerged on the research chemical market, and its hydroxy metabolite were tentatively identified by accurate mass, isotope matching, and plausible fragmentation. However, for unequivocal confirmation and quantification, a reference standard is required. As no reference material was available by the end of 2019, SL-164 was obtained from an online shop, and its identity and purity (97.8%) were confirmed by nuclear magnetic resonance spectroscopy. The subsequent quantitative analysis revealed a concentration of 390 ng/mL SL-164 in serum. In the urine sample, the parent compound was not detected, but three suspected monohydroxylated metabolites were found. This example shows that LC-QTOF-MS is a powerful approach for the (tentative) identification of unknown compounds in biological matrices.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124365","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
Human phase-I metabolism of three synthetic cannabinoids bearing a cumyl moiety and a cyclobutyl methyl or norbornyl methyl tail: Cumyl-CBMEGACLONE, Cumyl-NBMEGACLONE, and Cumyl-NBMINACA. 含有积基分子和环丁基甲基或降冰片基甲基尾部的三种合成大麻素的人体第一阶段代谢:Cumyl-CBMEGACLONE、Cumyl-NBMEGACLONE 和 Cumyl-NBMINACA。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-09-01 DOI: 10.1002/dta.3791
Arianna Giorgetti, Pietro Brunetti, Belal Haschimi, Benedikt Pulver, Jennifer Paola Pascali, Jan Riedel, Volker Auwärter
{"title":"Human phase-I metabolism of three synthetic cannabinoids bearing a cumyl moiety and a cyclobutyl methyl or norbornyl methyl tail: Cumyl-CBMEGACLONE, Cumyl-NBMEGACLONE, and Cumyl-NBMINACA.","authors":"Arianna Giorgetti, Pietro Brunetti, Belal Haschimi, Benedikt Pulver, Jennifer Paola Pascali, Jan Riedel, Volker Auwärter","doi":"10.1002/dta.3791","DOIUrl":"https://doi.org/10.1002/dta.3791","url":null,"abstract":"<p><p>Synthetic cannabinoid receptor agonists (SCRAs) continue to show high prevalence on the new psychoactive substances drug market. Around 2019-2020, new SCRAs bearing a cumyl moiety emerged: Cumyl-CBMEGACLONE and Cumyl-NBMEGACLONE, carrying a cyclobutyl methyl (CBM) and a norbornyl methyl moiety (NBM) attached to the γ-carbolinone core. These were followed by Cumyl-NBMINACA, the indazole carboxamide analog of Cumyl-NBMEGACLONE. The study aimed at evaluating the human phase-I metabolism of these compounds and at identifying suitable urinary markers to prove their consumption. After enzymatic hydrolysis, 14 authentic urine samples (eight for Cumyl-CBMEGACLONE, four for Cumyl-NBMEGACLONE, and two for Cumyl-NBMINACA) were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Results were compared with in vitro metabolites generated by pooled human liver microsomes incubation. Fifteen human phase-I metabolites were identified for Cumyl-CBMEGACLONE, nine for Cumyl-NBMEGACLONE, and thirteen for Cumyl-NBMINACA. The main in vivo metabolites were built by monohydroxylation, dihydroxylation, or trihydroxylation. The following urinary biomarkers are suggested for detecting the consumption of the investigated SCRAs: products of monohydroxylation at the CBM and at the core for Cumyl-CBMEGACLONE; two products of monohydroxylation at the norbonyl methyl tail for Cumyl-NBMEGACLONE; and metabolites built by dihydroxylation at the NBM substructure and by an additional hydroxylation at the cumyl moiety for Cumyl-NBMINACA.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102625","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
Characterization of the thyroid hormones level in urine by liquid chromatography coupled to mass spectrometry focus in the antidoping field. 利用液相色谱-质谱联用技术分析尿液中的甲状腺激素水平,重点关注反兴奋剂领域。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-24 DOI: 10.1002/dta.3788
Dayamin Martínez Brito, Patrizia Leogrande, Xavier de la Torre, Francesco Romanelli, Francesco Botrè
{"title":"Characterization of the thyroid hormones level in urine by liquid chromatography coupled to mass spectrometry focus in the antidoping field.","authors":"Dayamin Martínez Brito, Patrizia Leogrande, Xavier de la Torre, Francesco Romanelli, Francesco Botrè","doi":"10.1002/dta.3788","DOIUrl":"https://doi.org/10.1002/dta.3788","url":null,"abstract":"<p><p>This paper aims to study the metabolism of thyroid hormones (TH) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was applied to samples collected before and after the administration of sodium triiodothyronine (T3) and sodium levothyroxine (T4) to a euthyroid volunteer and to samples of athletes declaring and not declaring thyroid supplementation. Samples were analyzed by LC-MS/MS after enzymatic hydrolysis, liquid-liquid, and solid-phase extractions. Ratios between T3/thyronine and T4/3,3'-T2 may be used for the detection of the administration of exogenous T3 in urine. Meanwhile, 3-T1 concentrations may be used to detect exogenous T4 administration. Nevertheless, these markers may not work properly in hypothyroid population, as athletes seem to be. The levels of T3 and T4 of athletes were lower than those of a euthyroid state even when they are under administration of TH supplements. The HTP axis high efficiency does not allow observing differences between athletes who do not declare and those who declare having used TH supplementation by direct measurements of T3 and T4 in urine. The detection of TH administration in urine (triiodothyronine and levothyroxine) may work when dealing with euthyroid individuals. Nevertheless, in individuals with hypothyroidism where the tendency is toward the maintenance of homeostasis, and it may be not possible to detect their consumption by applying cut-off values.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046030","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
Changing trends in anabolic-androgenic steroid use within Scottish prisons: Detection, prevalence, and quantitation. 苏格兰监狱中合成代谢类固醇使用的变化趋势:检测、流行和定量。
IF 2.6 3区 医学
Drug Testing and Analysis Pub Date : 2024-08-20 DOI: 10.1002/dta.3790
Caitlyn Norman, Richard L Harries, Robert Reid, Lorna A Nisbet, Niamh Nic Daéid
{"title":"Changing trends in anabolic-androgenic steroid use within Scottish prisons: Detection, prevalence, and quantitation.","authors":"Caitlyn Norman, Richard L Harries, Robert Reid, Lorna A Nisbet, Niamh Nic Daéid","doi":"10.1002/dta.3790","DOIUrl":"https://doi.org/10.1002/dta.3790","url":null,"abstract":"<p><p>Anabolic-androgenic steroids (AASs) are a subclassification of image performance enhancing drugs (IPEDs). While AAS use is most prevalent among people in athletics, there is also high lifetime prevalence of AAS use among prisoners. This study reports the qualitative detection of AASs in seized samples from the Scottish prisons from 2019-2023. Additionally, methods were developed for the quantitative analysis of AASs using gas chromatography-mass spectrometry (GC-MS) and applied to 61 samples of tablets or powders seized from Scottish prisons between July 2022 and July 2023. Since 2022, there has been an increase in AAS detections in the Scottish prisons. Oxymetholone was the most prevalent AAS, followed by metandienone (methandrostenolone, methandienone), methyltestosterone, oxandrolone, mestanolone (methylandrostanolone), stanozolol, and androstenedione. Multiple AASs were found in 21 samples and 10 samples contained other drugs, including amitriptyline, sertraline, zopiclone, mirtazapine, sildenafil, etizolam, Δ<sup>9</sup>-tetrahydrocannabinol, and the synthetic cannabinoid MDMB-INACA. Most AAS samples were tablets (77.0%), although they were also detected in powders, herbal material, e-cigarettes, and a fragmented soap bar-type sample. There was a large variation in the concentration of AASs in the tablets and powders seized from the Scottish prisons, demonstrating AASs are another highly variable component of the polydrug use situation in prisons, the effects of which need to be examined further.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003102","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
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
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