Testing for Meldonium, a Doping Agent, in Human Hair.

IF 2.7 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Pascal Kintz, Jean-Claude Alvarez, Laurie Gheddar
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Abstract

Meldonium has been developed in the 70s in Latvia and is currently used in a limited number of countries for heart-related diseases, such as heart attack, failure, or angina pectoris. Due to its metabolic properties (decrease of lactate production, increase of glycogen use, and protective action again oxidative stress), meldonium has been abused by numerous athletes to enhance their performance. The drug has been prohibited by the World Anti-Doping Agency since 2016 and is on the S4.4.3 list (metabolic modulators) of the prohibited substances at all times. As athletes can challenge their anti-doping violation involving meldonium, there is an interest in testing for it in hair in order to document their pattern of exposure. Such hair application can be complicated to develop, as meldonium has a chemical formula close to an amino acid and presents an ionized fraction, which are limiting factors for drug incorporation into hair. Liquid chromatography coupled to tandem mass spectrometry was used. The drug was extracted from hair after methanol incubation in an ultrasound bath and separation on a BEH HILIC column. Linearity was verified from 0.5 to 100 pg/mg (R2 = 0.9943). The limit of detection was 0.1 pg/mg. Although their meldonium regimen was unknown, the drug was identified in the proximal hair segment (0 to 1 cm) of three consumers at 0.7, 6.1, and 17 pg/mg, highlighting for the first time the incorporation in hair of this molecule.

在人类头发中检测兴奋剂米屈肼。
美度铵是70年代在拉脱维亚开发的,目前在少数国家用于治疗心脏病、心力衰竭或心绞痛等与心脏有关的疾病。由于其代谢特性(减少乳酸生成,增加糖原使用,并对氧化应激有保护作用),米屈肼被许多运动员滥用以提高他们的表现。自2016年以来,该药物一直被世界反兴奋剂机构禁止使用,并且一直在禁用物质的S4.4.3列表(代谢调节剂)中。由于运动员可以对自己违反反兴奋剂规定提出质疑,因此有兴趣在头发中检测米屈肼,以记录他们的暴露模式。这种毛发应用开发起来很复杂,因为米屈肼的化学式接近于氨基酸,并呈现电离部分,这是药物进入头发的限制因素。采用液相色谱-串联质谱联用。在超声波浴中甲醇孵育后,在BEH - HILIC柱上分离,从头发中提取药物。线性范围为0.5 ~ 100 pg/mg (R2 = 0.9943)。检出限为0.1 pg/mg。虽然他们的米屈肼治疗方案是未知的,但该药物在三个消费者的近端头发节(0至1厘米)中被鉴定为0.7,6.1和17 pg/mg,首次突出了该分子在头发中的掺入。
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来源期刊
Drug Testing and Analysis
Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
5.90
自引率
24.10%
发文量
191
审稿时长
2.3 months
期刊介绍: As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.
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