Drug Testing and Analysis最新文献_第5页

Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares. 给母马服用的两种 Altrenogest 制剂的药代动力学。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-22 DOI: 10.1002/dta.3796

Jaymie Loy, Adam Cawley, Kireesan Sornalingam, Colin J Scrivener, John Keledjian, Glenys K Noble

{"title":"Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares.","authors":"Jaymie Loy, Adam Cawley, Kireesan Sornalingam, Colin J Scrivener, John Keledjian, Glenys K Noble","doi":"10.1002/dta.3796","DOIUrl":"https://doi.org/10.1002/dta.3796","url":null,"abstract":"Altrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determining accurate dosing and detection intervals, pharmacokinetic analysis using mares is required. Blood samples were taken from 10 mares pretreatment to obtain baseline concentrations. Mares were administered altrenogest, either oral (PO; 0.044 mg/kg; daily for 15 days) or intramuscular (IM; 0.3 mg/kg; twice; Days 0 and 7). On the first and last treatment day, blood samples were taken at designated times post dosing. After a 3-week washout, mares received the alternative treatment with sampling repeated. At the initial dose, for IM administration mean (± SD) plasma altrenogest Cmax was 18.0 ± 6.6 ng/mL at 7.9 ± 3.9 h compared with PO dosing 13.2 ± 5.8 ng/mL at 0.8 ± 0.8 h. Plasma Cmax on the final day was significantly higher (p = 0.002 [IM]; p = 0.006 [PO]). At 24 h post final oral treatment, mean (± SD) plasma altrenogest was 1.0 ± 0.8 ng/mL and at 48 h were 0.65 ± 0.5 ng/mL. Plasma concentrations well exceeding this may indicate that the one clear day rule or dosage recommendations have not been adhered to.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277631","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

Discovery of Biomarkers of a Recombinant Human Erythropoietin Administration to Thoroughbred Geldings by Label-Free Proteomics. 通过无标记蛋白质组学发现纯血马骟马使用重组人促红细胞生成素的生物标记物

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-22 DOI: 10.1002/dta.3810

Hiu Wing Cheung, Kin-Sing Wong, Jimmy C L Tam, Adrian F Farrington, Amanda J Bond, Terence S M Wan, Emmie N M Ho

{"title":"Discovery of Biomarkers of a Recombinant Human Erythropoietin Administration to Thoroughbred Geldings by Label-Free Proteomics.","authors":"Hiu Wing Cheung, Kin-Sing Wong, Jimmy C L Tam, Adrian F Farrington, Amanda J Bond, Terence S M Wan, Emmie N M Ho","doi":"10.1002/dta.3810","DOIUrl":"https://doi.org/10.1002/dta.3810","url":null,"abstract":"Erythropoiesis-stimulating agents (ESAs) continue to be a significant threat to the integrity of human and equine sports. Besides conventional direct testing, monitoring the biomarkers associated with the effects of ESAs may provide a complementary approach via indirect detection to enhance doping control. In this study, we applied label-free proteomics to discover plasma protein biomarkers in Thoroughbred geldings after administration with a long-acting form of recombinant human erythropoietin (rhEPO), methoxy polyethylene glycol epoetin beta, Mircera. Increased haematocrit, haemoglobin and red blood cell (RBC) levels were evidenced as early as 4 days post-administration in all three horses to varying extents. Tryptic peptides were obtained from plasma samples and analysed by nanoflow ultra-high-performance liquid chromatography-high-resolution tandem mass spectrometry (nano-UHPLC-HRMSMS) using data-independent acquisition. Differential protein abundance analysis has shortlisted seven protein biomarker candidates that showed significant changes specifically after Mircera administration in the treated but not in the control geldings, which comprised downregulation of two proteins, haptoglobin (HP) and haemopexin (HPX), and upregulation of five proteins, transferrin receptor 1 (TFR1), phospholipid transfer protein (PLTP), tenascin C (TNC), vascular cell adhesion molecule 1 (VCAM1) and galectin 3 binding protein (LGALS3BP). Multivariate analysis of plasma proteome has allowed the classification of control and treated samples. This is the first report on the discovery of plasma protein biomarkers of rhEPO administration to geldings. The results lay a foundation for applications of protein biomarkers for controlling the misuse of ESAs.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277607","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

High-Throughput Equine Doping Controls on a Trapped Ion Mobility Quadrupole-Time-of-Flight Mass Spectrometer: Technical Considerations of dia/slice/prmPASEF Applied to the Long-Term Detection of Monoclonal Antibodies. 利用捕获离子迁移率四极杆-飞行时间质谱仪进行高通量马匹兴奋剂控制：应用 dia/slice/prmPASEF 对单克隆抗体进行长期检测的技术考虑。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-22 DOI: 10.1002/dta.3797

Vivian Delcourt, Justine Pinetre, Benjamin Chabot, Agnès Barnabé, Marie Cacault, Benoit Loup, François Becher, François Fenaille, Marie-Agnès Popot, Patrice Garcia, Ludovic Bailly-Chouriberry

{"title":"High-Throughput Equine Doping Controls on a Trapped Ion Mobility Quadrupole-Time-of-Flight Mass Spectrometer: Technical Considerations of dia/slice/prmPASEF Applied to the Long-Term Detection of Monoclonal Antibodies.","authors":"Vivian Delcourt, Justine Pinetre, Benjamin Chabot, Agnès Barnabé, Marie Cacault, Benoit Loup, François Becher, François Fenaille, Marie-Agnès Popot, Patrice Garcia, Ludovic Bailly-Chouriberry","doi":"10.1002/dta.3797","DOIUrl":"https://doi.org/10.1002/dta.3797","url":null,"abstract":"Data-independent acquisition (DIA) methods employing a scanning quadrupole were recently described across multiple platforms. These strategies display remarkable performances in untargeted proteomics studies thanks to rapid duty cycles, leading to ultrashort liquid chromatography gradients while maintaining enough data points per peaks when coupled to fast-scanning mass analyzer. In this article, we perform the evaluation of three data acquisition strategies named diaPASEF,slicePASEF, and prmPASEF on a trapped ion mobility spectrometry quadrupole-time-of-flight (TIMS-Q-TOF) mass spectrometer for high-throughput doping control screening analyses. We report that slicePASEF outperforms diaPASEF and is almost as sensitive as prmPASEF in detecting humanized monoclonal antibodies for several weeks in equine plasma after administration. We observed that diaPASEF is still providing the best performances in untargeted proteomics studies employing high amounts of input materials, which is linked with the high complexity of slicePASEF data and current processing algorithms.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277611","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

Emerging Human Medications in Racing Animals: Analytical and Regulatory Challenges. 赛马动物中新出现的人类药物：分析和监管挑战。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-19 DOI: 10.1002/dta.3805

Buddhika N Dorakumbura, Nicola M Beckett, Elise C Cook, Ashley-N' Dene Nolan, David Brown, Bianca Douglas

{"title":"Emerging Human Medications in Racing Animals: Analytical and Regulatory Challenges.","authors":"Buddhika N Dorakumbura, Nicola M Beckett, Elise C Cook, Ashley-N' Dene Nolan, David Brown, Bianca Douglas","doi":"10.1002/dta.3805","DOIUrl":"https://doi.org/10.1002/dta.3805","url":null,"abstract":"Positive identification and reporting of therapeutic substances intended for human consumption in race-day equine and canine samples is a controversial topic. While inadvertent environmental exposure is a potential cause for the presence of these substances in race-day samples, intentional use cannot be ruled out given their therapeutic benefits. Pregabalin is widely prescribed in Australia to treat epilepsy, anxiety, and neuropathic pain in humans; however, it is also increasingly used as a recreational drug. Metformin is commonly used to treat type 2 diabetes in humans. Both pregabalin and metformin have no routine use on racing animals and should not be present in race-day samples taken from healthy animals. They are prohibited substances under the Rules of Racing with no established screening limits. Although therapeutic levels for these substances have been established in humans, such information is not available for animals. Pregabalin and metformin are analytically challenging molecules, more so when they are extracted from biological matrices routinely screened for hundreds of other compounds simultaneously. A simple extraction, followed by a targeted Ultra High-Pressure Liquid Chromatography Orbitrap™ Mass Spectrometry method utilising a reverse-phase C18 column, is presented. This method is effective in screening for pregabalin and metformin, in addition to more than 150 other compounds of interest in equine and canine urines. The prevalence of pregabalin and metformin in race-day equine and canine urine samples in Western Australia was monitored using this method over 12 months. More than 4000 urine samples were screened, and four samples were confirmed positive for these substances.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277608","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

Doping Control Analysis of Perfluorocarbons in Equine Plasma by Headspace Gas Chromatography-Tandem Mass Spectrometry. 利用顶空气相色谱-串联质谱法对马血浆中的全氟化碳进行兴奋剂控制分析。

IF 2.9 3区医学

Drug Testing and Analysis Pub Date : 2024-09-18 DOI: 10.1002/dta.3801

Fred K W Kong,April S Y Wong,Raymond K K Cheung,Terence S M Wan,Emmie N M Ho

引用次数: 0

Interest of Hair Tests to Discriminate a Tail End of a Voluntary Doping Regimen From the Use of a Contaminated Medicine in Case of Challenging an Antidoping Rule Violation. VI. Case Example With Trimetazidine 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自愿使用兴奋剂疗程的结束与受污染药物的使用。VI.曲美他嗪案例

IF 2.9 3区医学

Drug Testing and Analysis Pub Date : 2024-09-17 DOI: 10.1002/dta.3808

Pascal Kintz, Laurie Gheddar

引用次数: 0

When Oxybutynin Becomes a Decoy for Oxycodone: A Case Report of Diversion Through Substitution 当奥昔布宁成为奥昔可酮的诱饵时：通过替代品转移用途的案例报告

IF 2.9 3区医学

Drug Testing and Analysis Pub Date : 2024-09-17 DOI: 10.1002/dta.3802

Ricardo E. Verdiner, Alissa Voils, Lynsey Seim, Krystal Koball, Maxwell Verdiner, Aram Mardian, Adam J. Milam

引用次数: 0

Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum. 改进人血清中内源性类固醇碳同位素比值的测定。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-16 DOI: 10.1002/dta.3793

Thomas Piper, Mario Thevis

{"title":"Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum.","authors":"Thomas Piper, Mario Thevis","doi":"10.1002/dta.3793","DOIUrl":"https://doi.org/10.1002/dta.3793","url":null,"abstract":"The determination of serum concentrations of testosterone (T) and 4-androstenedione (A4) was implemented into the steroidal module of the Athlete Biological Passport in 2023. Monitoring T, A4, and the ratio of T/A4 in a longitudinal manner enables the detection of the misuse of low-dose T administrations especially in female athletes, whereas urinary markers of the steroid profile may not be influenced significantly. In contrast to the urinary steroid profile, knowledge on confounding factors regarding serum concentrations of T and A4 is yet comparably scarce, and corroborating exogenous sources of the target analytes by isotope ratio mass spectrometry (IRMS) is desirable. In a recent study, it was demonstrated that carbon isotope ratios (CIRs) of serum steroids can be determined if analyte concentrations permit. The therein-employed method utilized 2D-GC/IRMS, and only a limited number of potential endogenous reference compounds were available. The here-presented approach uses complementary analyte purification strategies, addressing previous limitations. A high-performance liquid chromatography cleanup was developed and fully validated for serum steroids in order to enable all doping control laboratories to potentially implement this method alongside existing protocols for urinary steroids. Besides the already-investigated endogenous steroids cholesterol, dehydroepiandrosterone sulfate, androsterone sulfate, and epiandrosterone sulfate, two additional steroids were included in the test menu, namely, pregnenolone sulfate and 5-androstene-3β,17β-diol sulfate. Serum steroid concentrations down to 25 ng/mL were found to allow robust CIR determinations, and a reference population encompassing 124 male and female athlete samples was investigated to enable the calculation of population-based thresholds for all relevant steroid combinations.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277628","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

Bayesian Individual Limits for IGF-1 Monitoring in Equine Plasma: Implementation in the Equine Biological Passport. 马血浆中 IGF-1 监测的贝叶斯个体限值：在马生物护照中的实施。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-16 DOI: 10.1002/dta.3795

Agnès Barnabé, Benoit Loup, Adam Cawley, Vivian Delcourt, Patrice Garcia, Marie-Agnès Popot, John Keledjian, Ludovic Bailly-Chouriberry

{"title":"Bayesian Individual Limits for IGF-1 Monitoring in Equine Plasma: Implementation in the Equine Biological Passport.","authors":"Agnès Barnabé, Benoit Loup, Adam Cawley, Vivian Delcourt, Patrice Garcia, Marie-Agnès Popot, John Keledjian, Ludovic Bailly-Chouriberry","doi":"10.1002/dta.3795","DOIUrl":"https://doi.org/10.1002/dta.3795","url":null,"abstract":"Despite the International Federation of Horseracing Authorities (IFHA) regulation associated with heavy sanctions, the abuse of prohibited substances must be identified and deterred throughout horses' athletic careers, such as the administration of recombinant growth hormone (rGH). GH is naturally produced in mammal organisms to stimulate growth. Thus, rGH administration can enhance the performance of horses by expanding some physical abilities. As measuring endogenous GH levels is complex, an indirect strategy is to monitor GH-associated biomarkers in plasma as insulin-like growth factor 1 (IGF-1) levels. To prevent these misuses, the Equine Biological Passport (EBP) has been designed in France (GIE LCH) and Australia (ARFL-Racing NSW) to profile specific biological and chemical parameters in selected racehorses. In this study, we investigated individual limits as a complementary tool to a single limit to supervise the stability of IGF-1 profile over a racing season. The aim is to design custom limits based on the horse's history to detect any deviation below the single limit. The method was assessed using experimental data and then tested on EBP data from three thoroughbreds and three French trotters. Finally, individual limits have been added to the French EBP for IGF-1 monitoring.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277605","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

Evaluating the Effects of Solid-Phase Cartridge Chemistry on Extraction of Bisphosphonates and ITPP From Equine Plasma. 评估固相滤芯化学法对从马血浆中提取双膦酸盐和 ITPP 的影响。

IF 2.6 3区医学

Drug Testing and Analysis Pub Date : 2024-09-16 DOI: 10.1002/dta.3800

Joshua Klingberg, Stacey Richards, Travis Hochwallner, Lauren Kennan, John Keledjian

引用次数: 0