探索通过皮肤的SARM暴露:分析用于兴奋剂控制目的的消除概况和代谢
Linus Korsmeier1, Sophia Krombholz1, Hana Alhalabi1
1Center for Preventive Doping Research/Institute of Biochemistry, German Sport University, Cologne, Am Sportpark Müngersdorf 6, Cologne, 50933, Germany.
选择性雄激素受体调节剂 (SARMs) 的通过皮肤递送药物可以导致体育药物测试中的不良分析结果. 即使在皮肤上施加的微剂量也可以在尿液中检测到,这突显了污染的风险.
科学领域:
- 运动科学 运动科学 运动科学
- 药理学 药理学是指药理学的学科.
- 分析化学 分析化学
背景情况:
- 通过皮肤递送药物对制药研究和体育药物测试具有重要意义.
- 选择性雄激素受体调节剂 (SARMs) 的意外口服可能导致不良分析结果 (AAF).
- 皮肤暴露为SARM吸收提供了另一条途径,透取决于物质特性.
研究的目的:
- 模拟通过皮肤的SARM污染.
- 为了研究LGD-4033,RAD140和S-23微剂量的皮肤透和代谢.
- 评估皮肤SARM暴露导致AAFs的风险.
主要方法:
- 给5名志愿者的前臂注射了10或50μg的LGD-4033,RAD140和S-23.
- 在酶水解和固相提取后,使用LC-MS/MS进行尿样分析.
- 高灵敏度检测 (对于LGD-4033和S-23的≥5ppg/ml).
主要成果:
- 在10μg应用后检测到LGD-4033和S-23;RAD140仅在一个受试者中检测到.
- 在50μg的应用后,RAD140在所有受试者中被检测到长达9天.
- 确定了所有三种SARM的代谢物,长期检测LGD-4033 (M5b) 和S-23代谢物长达25天.
结论:
- 这三种研究的SARM都能穿透皮肤.
- 通过皮肤给予SARM,即使是微量,也可能导致AAFs.
- 尿液SARM数据有助于解释与皮肤暴露或故意兴奋剂相关的AAF.
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