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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 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-22 DOI: 10.1002/dta.3796
Jaymie Loy, Adam Cawley, Kireesan Sornalingam, Colin J Scrivener, John Keledjian, Glenys K Noble

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.

Altrenogest 是一种合成孕激素,可抑制雌马的生殖行为并帮助维持妊娠。目前有两种配方,一种是 "每周 "肌肉注射配方,另一种是每日口服配方。使用阿孕酮后,类固醇拭子检测结果呈阳性;因此,禁止在赛马中使用注射用阿孕酮。如果在给药和比赛之间有一个晴朗的日子,则允许赛马母马口服给药。目前仅有的药代动力学数据来自骟马。因此,为了帮助兽医和分析人员确定准确的剂量和检测时间间隔,需要使用母马进行药代动力学分析。我们从 10 头母马身上采集了预处理血液样本,以获得基线浓度。给母马口服(PO;0.044 mg/kg;每天,共 15 天)或肌肉注射(IM;0.3 mg/kg;两次;第 0 天和第 7 天)阿替孕酮。在第一个和最后一个治疗日,在用药后的指定时间采集血液样本。经过 3 周的冲洗后,母马接受另一种治疗,并重复采样。初始给药时,IM 给药的平均(± SD)血浆阿替孕酮 Cmax 为 18.0 ± 6.6 纳克/毫升(7.9 ± 3.9 小时),而 PO 给药的平均(± SD)血浆 Cmax 为 13.2 ± 5.8 纳克/毫升(0.8 ± 0.8 小时)。在最后一次口服治疗后 24 小时,阿替诺孕酮的平均(± SD)血浆浓度为 1.0 ± 0.8 纳克/毫升,48 小时为 0.65 ± 0.5 纳克/毫升。血浆浓度远高于此值可能表明没有遵守 "一天一清 "的规定或剂量建议。
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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

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.

促红细胞生成素(ESAs)仍然是对人类和马匹运动完整性的重大威胁。除了传统的直接检测外,监测与 ESAs 作用相关的生物标志物也是一种通过间接检测加强兴奋剂控制的补充方法。在这项研究中,我们应用无标记蛋白质组学发现了纯血马骟马在服用长效重组人促红细胞生成素(rhEPO)(甲氧基聚乙二醇环氧乙烷 beta,Mircera)后的血浆蛋白生物标记物。早在给药后 4 天,三匹马的血细胞比容、血红蛋白和红细胞(RBC)水平就出现了不同程度的升高。从血浆样本中提取了胰蛋白酶肽,并通过纳米流超高效液相色谱-高分辨串联质谱法(nano-UHPLC-HRMSMS)进行了分析,该方法采用了数据独立采集技术。差异蛋白质丰度分析筛选出了七种候选蛋白质生物标记物,这些标记物在治疗组骟马服用 Mircera 后发生了显著变化,而对照组骟马则没有,其中包括两种蛋白质的下调、转铁蛋白受体 1 (TFR1)、磷脂转移蛋白 (PLTP)、腱鞘蛋白 C (TNC)、血管细胞粘附分子 1 (VCAM1) 和半连接蛋白 3 结合蛋白 (LGALS3BP) 五种蛋白质上调。通过对血浆蛋白质组进行多变量分析,可以对对照样本和治疗样本进行分类。这是首次报道发现骟马服用 rhEPO 的血浆蛋白生物标志物。这些结果为应用蛋白质生物标志物控制ESAs的滥用奠定了基础。
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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

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.

采用扫描四极杆的数据独立采集(DIA)方法最近在多个平台上得到了应用。这些策略在非靶向蛋白质组学研究中表现出卓越的性能,这得益于其快速的工作周期,当与快速扫描质量分析仪联用时,可实现超短的液相色谱梯度,同时每个峰保持足够的数据点。在本文中,我们在用于高通量掺杂控制筛选分析的阱式离子迁移谱四极杆飞行时间(TIMS-Q-TOF)质谱仪上评估了三种数据采集策略(diaPASEF、slicePASEF和prmPASEF)。我们报告说,在检测马血浆中的人源化单克隆抗体方面,slicePASEF 优于 diaPASEF,其灵敏度几乎与 prmPASEF 相当。我们发现,在使用大量输入材料的非靶向蛋白质组学研究中,diaPASEF 仍能提供最佳性能,这与 slicePASEF 数据的高复杂性和当前的处理算法有关。
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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

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.

赛马和赛犬样本中供人类食用的治疗药物的阳性鉴定和报告是一个有争议的话题。虽然无意中的环境暴露是比赛日样本中出现这些物质的潜在原因,但鉴于其治疗功效,也不能排除有意使用的可能性。普瑞巴林在澳大利亚被广泛用于治疗人类的癫痫、焦虑和神经性疼痛;然而,它也越来越多地被用作一种娱乐性药物。二甲双胍通常用于治疗人类的 2 型糖尿病。普瑞巴林和二甲双胍都不能在赛马动物身上常规使用,也不应出现在从健康动物身上采集的比赛日样本中。根据《赛马规则》,这两种药物属于禁用物质,没有规定筛查限值。虽然这些物质在人体中的治疗水平已经确定,但在动物中却没有此类信息。普瑞巴林和二甲双胍是极具分析挑战性的分子,当它们从同时筛查数百种其他化合物的生物基质中提取时,挑战性就更大了。本研究介绍了一种简单的提取方法,然后利用反相 C18 色谱柱进行有针对性的超高压液相色谱 Orbitrap™ 质谱分析。该方法可有效筛查马和犬尿液中的普瑞巴林和二甲双胍以及其他 150 多种相关化合物。使用该方法对西澳大利亚州赛马和赛犬尿样中普瑞巴林和二甲双胍的含量进行了为期 12 个月的监测。共筛查了 4000 多份尿液样本,其中 4 份样本被证实对这两种物质呈阳性反应。
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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
In order to control the potential misuse of perfluorocarbons as an oxygen carrier in equine sports, a simple and sensitive method for detecting perfluorocarbons in equine plasma by gas chromatography/tandem mass spectrometry using negative chemical ionization with methane as reagent gas has been developed and fully validated. The method covers seven perfluorocarbons, which are the active components in blood substitute products, and shows good sensitivity and robustness. Limits of detection as low as 0.01 ng/mL could be achieved by the method. To the best of our knowledge, this is the first report of a detection method for the screening of perfluorocarbons in equine biological samples.
为了控制马匹运动中可能滥用全氟化碳作为氧气载体的情况,我们开发了一种简单灵敏的方法,以甲烷为试剂气体,利用负化学电离的气相色谱/串联质谱法检测马血浆中的全氟化碳,并进行了全面验证。该方法涵盖了血液替代产品中的七种活性成分--全氟化碳,具有良好的灵敏度和稳健性。该方法的检测限低至 0.01 纳克/毫升。据我们所知,这是首次报道用于筛查马生物样本中全氟碳化物的检测方法。
{"title":"Doping Control Analysis of Perfluorocarbons in Equine Plasma by Headspace Gas Chromatography-Tandem Mass Spectrometry.","authors":"Fred K W Kong,April S Y Wong,Raymond K K Cheung,Terence S M Wan,Emmie N M Ho","doi":"10.1002/dta.3801","DOIUrl":"https://doi.org/10.1002/dta.3801","url":null,"abstract":"In order to control the potential misuse of perfluorocarbons as an oxygen carrier in equine sports, a simple and sensitive method for detecting perfluorocarbons in equine plasma by gas chromatography/tandem mass spectrometry using negative chemical ionization with methane as reagent gas has been developed and fully validated. The method covers seven perfluorocarbons, which are the active components in blood substitute products, and shows good sensitivity and robustness. Limits of detection as low as 0.01 ng/mL could be achieved by the method. To the best of our knowledge, this is the first report of a detection method for the screening of perfluorocarbons in equine biological samples.","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":"31 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257607","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 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 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-17 DOI: 10.1002/dta.3808
Pascal Kintz, Laurie Gheddar
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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
This case report describes the novel use of oxybutynin and acetaminophen as a substitution for oxycodone for the express purpose of diverting oxycodone in a hospital‐based post‐anesthesia care unit (PACU). The report outlines how the physical properties and pharmacologic effects of non‐controlled medications in the PACU, like oxybutynin, can be visually mistaken and even mimic the side effects of controlled substances like oxycodone. Substituting oxybutynin for controlled substances can circumvent diversion surveillance software. The authors describe how the diversion was identified and the process improvements that should be implemented for proactive identification moving forward.
本病例报告描述了在医院麻醉后护理病房(PACU)中使用奥昔布宁和对乙酰氨基酚作为羟考酮替代品的新情况,其明确目的是转移羟考酮。报告概述了 PACU 中非管制药物(如羟丁宁)的物理性质和药理作用如何被误认为甚至模仿受管制药物(如羟考酮)的副作用。用奥昔布宁代替受管制药物可以规避转移监控软件。作者介绍了如何识别出转移用途的情况,以及今后在主动识别方面应实施的流程改进。
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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 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-16 DOI: 10.1002/dta.3793
Thomas Piper, Mario Thevis

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.

睾酮(T)和 4-雄烯二酮(A4)血清浓度的测定于 2023 年纳入运动员生物护照的类固醇模块。纵向监测睾酮、4-雄烯二酮和睾酮/4-雄烯二酮的比值可以发现滥用小剂量睾酮的情况,尤其是女运动员,而尿液中的类固醇指标可能不会受到明显影响。与尿液类固醇概况相比,有关血清中 T 和 A4 浓度的混杂因素的知识还相当匮乏,因此需要通过同位素比质谱法(IRMS)来证实目标分析物的外源性来源。最近的一项研究表明,如果分析物浓度允许,可以测定血清类固醇的碳同位素比值(CIR)。该研究采用的方法是 2D-GC/IRMS 方法,而且只有有限的潜在内源性参考化合物可用。本文介绍的方法采用互补的分析纯化策略,解决了以前的局限性。针对血清类固醇开发并全面验证了一种高效液相色谱净化方法,以使所有兴奋剂检测实验室都能在采用现有尿液类固醇检测方案的同时采用该方法。除了已经检测过的内源性类固醇胆固醇、硫酸脱氢表雄酮、硫酸雄甾酮和硫酸表雄酮外,检测菜单中还增加了两种类固醇,即硫酸孕烯醇酮和硫酸 5-雄烯-3β,17β-二醇。研究发现,血清类固醇浓度低至 25 毫微克/毫升时,也能进行可靠的 CIR 测定,并对包含 124 个男女运动员样本的参考人群进行了调查,以便能够计算出所有相关类固醇组合的人群阈值。
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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 Q2 BIOCHEMICAL RESEARCH METHODS 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

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.

尽管国际赛马管理机构联合会(IFHA)规定了严厉的处罚措施,但在马匹的整个运动生涯中,必须识别和阻止滥用禁用物质的行为,例如使用重组生长激素(rGH)。生长激素是哺乳动物体内自然产生的一种刺激生长的物质。因此,使用重组生长激素可以提高马匹的某些身体机能,从而提高马匹的运动表现。由于测量内源性 GH 水平非常复杂,一种间接的策略是监测血浆中与 GH 相关的生物标志物,如胰岛素样生长因子 1 (IGF-1) 水平。为了防止这些误用,法国(GIE LCH)和澳大利亚(ARFL-Racing NSW)设计了马匹生物护照(EBP),对选定赛马的特定生物和化学参数进行分析。在这项研究中,我们调查了作为单一限值补充工具的个体限值,以监督 IGF-1 在一个赛季中的稳定性。目的是根据赛马的历史记录设计定制限值,以检测任何低于单一限值的偏差。该方法利用实验数据进行了评估,然后在三匹纯血马和三匹法国小步赛马的 EBP 数据上进行了测试。最后,在法国 EBP 中添加了用于 IGF-1 监测的单个限值。
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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 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-16 DOI: 10.1002/dta.3800
Joshua Klingberg, Stacey Richards, Travis Hochwallner, Lauren Kennan, John Keledjian

Bisphosphonate drugs and myo-inositol trispyrophosphate are of concern to the racing industry and have been listed as prohibited substances in equine sports. The current bisphosphonate plasma screening analysis employed at the Australian Racing Forensic Laboratory involves the use of sequential solid-phase extraction procedures, passing the samples through a mixed mode cartridge, followed by a weak anion exchange cartridge. The eluates collected following the second extraction are then methylated and analysed by liquid chromatography-mass spectrometry. Under these extraction conditions, some bisphosphonates have shown poor recovery. To improve the extraction efficacy, the effects of cartridge chemistry were evaluated. In particular, the weak anion exchange cartridges used for screening were compared to an affinisep AttractSPE polymeric phase cartridge. The effectiveness of each extraction approach was assessed through both a visual comparison of signal to noise in extracted chromatograms and recovery measurements to determine the best approach for routine screening.

双膦酸盐药物和肌醇三异焦磷酸盐是赛马业关注的问题,已被列为马术运动的禁用物质。澳大利亚赛马法医实验室目前采用的双膦酸盐血浆筛查分析方法包括使用顺序固相萃取程序,将样品通过混合模式滤芯,然后再通过弱阴离子交换滤芯。第二次萃取后收集的洗脱液经过甲基化处理,然后用液相色谱-质谱法进行分析。在这种萃取条件下,某些双膦酸盐的回收率较低。为了提高萃取效率,我们对滤芯化学成分的影响进行了评估。特别是将用于筛选的弱阴离子交换柱与 affinisep AttractSPE 聚合相柱进行了比较。通过对萃取色谱中的信噪比和回收率进行直观比较,评估了每种萃取方法的效果,以确定用于常规筛选的最佳方法。
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引用次数: 0
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Drug Testing and Analysis
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