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在兴奋剂检测分析中使用气相色谱-质谱联用技术筛查两种选择性雄激素受体调节剂。

Screening for two selective androgen receptor modulators using gas chromatography-mass spectrometry in doping control analysis.

作者信息

Thevis Mario, Kohler Maxie, Schlörer Nils, Fusshöller Gregor, Schänzer Wilhelm

机构信息

Center for Preventive Doping Research-Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany.

出版信息

Eur J Mass Spectrom (Chichester). 2008;14(3):153-61. doi: 10.1255/ejms.917.

Abstract

Selective androgen receptor modulators (SARMs) have become a major field of clinical research enabling the tissue-selective stimulation of androgen receptors. The treatment of debilitating diseases, osteoporosis and frailty are primary goals and promising results have been obtained from clinical trials. However, the potential for misuse of SARMs in sport is great and drug testing methods based on liquid chromatography were established for different classes including arylpropionamide-, 2-quinolinone- and bicyclic hydantoin-derived compounds. As gas chromatography and mass spectrometry (GC-MS) are still important analytical tools in sports drug testing, a method to determine 2-quinolinone- and bicyclic hydantoin-derived SARMs established. Spiked urine samples were subjected to routine doping control protocols including enzymatic hydrolysis, liquid-liquid extraction, concentration and derivatisation to trimethylsilylated analogues followed by GC-MS analysis. The method was validated for the items specificity, lower limit of detection (0.2-10 ng mL(-1)), recovery (83-85%), intraday and interday precision (9-15% and 13-18%, respectively), which demonstrates the suitability of conventional GC-MS systems to determine representatives of an emerging class of compounds in doping control specimens.

摘要

选择性雄激素受体调节剂(SARMs)已成为临床研究的一个主要领域,能够实现对雄激素受体的组织选择性刺激。治疗衰弱性疾病、骨质疏松症和身体虚弱是主要目标,并且临床试验已取得了有前景的结果。然而,SARMs在体育界被滥用的可能性很大,基于液相色谱的药物检测方法已针对不同类别建立,包括芳基丙酰胺、2-喹啉酮和双环乙内酰脲衍生的化合物。由于气相色谱和质谱(GC-MS)仍是体育药物检测中的重要分析工具,一种测定2-喹啉酮和双环乙内酰脲衍生的SARMs的方法得以建立。加标尿液样本按照常规兴奋剂控制方案进行处理,包括酶促水解、液-液萃取、浓缩和衍生化为三甲基硅烷化类似物,随后进行GC-MS分析。该方法在项目特异性、检测下限(0.2 - 10 ng mL(-1))、回收率(83 - 85%)、日内和日间精密度(分别为9 - 15%和13 - 18%)方面得到了验证,这表明传统GC-MS系统适用于在兴奋剂控制样本中测定一类新兴化合物的代表物。

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