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Targeting prohibited substances in doping control blood samples by means of chromatographic–mass spectrometric methods

机译:通过色谱-质谱法确定掺杂对照血样中的违禁物质

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摘要

Urine samples have been the predominant matrix for doping controls for several decades. However, owing to the complementary information provided by blood (as well as serum or plasma and dried blood spots (DBS)), the benefits of its analysis have resulted in continuously increasing appreciation by anti-doping authorities. On the one hand, blood samples allow for the detection of various different methods of blood doping and the abuse of erythropoiesis-stimulating agents (ESAs) via the Athlete Biological Passport; on the other hand, targeted and non-targeted drug detection by means of chromatographic–mass spectrometric methods represents an important tool to increase doping control frequencies out-of-competition and to determine drug concentrations particularly in in-competition scenarios. Moreover, blood analysis seldom requires in-depth knowledge of drug metabolism, and the intact substance rather than potentially unknown or assumed metabolic products can be targeted. In this review, the recent developments in human sports drug testing concerning mass spectrometry-based techniques for qualitative and quantitative analyses of therapeutics and emerging drug candidates are summarized and reviewed. The analytical methods include both low and high molecular mass compounds (e.g., anabolic agents, stimulants, metabolic modulators, peptide hormones, and small interfering RNA (siRNA)) determined from serum, plasma, and DBS using state-of-the-art instrumentation such as liquid chromatography (LC)–high resolution/high accuracy (tandem) mass spectrometry (LC-HRMS), LC–low resolution tandem mass spectrometry (LC-MS/MS), and gas chromatography–mass spectrometry (GC-MS).
机译:几十年来,尿液样品一直是掺杂控制的主要基质。但是,由于血液(以及血清或血浆和干血斑(DBS))提供的补充信息,其分析的好处已导致反兴奋剂机构的赏识不断提高。一方面,血液样本可以通过运动员生物护照检测各种不同的血液掺杂方法和滥用红细胞生成刺激剂(ESA);另一方面,通过色谱-质谱法进行靶向和非靶向药物检测代表了一种重要的工具,可以提高非竞争性掺杂控制频率并确定药物浓度,尤其是在竞争中。此外,血液分析很少需要对药物代谢的深入了解,并且可以靶向完整物质而不是潜在未知或假定的代谢产物。在这篇综述中,总结并回顾了人类运动药物测试的最新进展,涉及基于质谱技术的定性和定量分析疗法和候选新兴药物的质谱技术。分析方法包括使用最先进的仪器从血清,血浆和DBS中测定的低分子量和高分子量化合物(例如合成代谢药物,兴奋剂,代谢调节剂,肽激素和小干扰RNA(siRNA))例如液相色谱(LC)–高分辨率/高精度(串联)质谱(LC-HRMS),LC –低分辨率串联质谱(LC-MS / MS)和气相色谱–质谱(GC-MS) 。

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