Saardpun Navaporn, Asawesna Cholsittapan, Kaewklam Seksun, Sangkhum Premsant, Kongchareonsombat Wisoot, Kusamran Thanit, Pinthong Darawan
National Doping Control Center (NDCC), Analytical Sciences and National Doping Test Institute (ANDI), Mahidol University, Bangkok, Thailand.
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Drug Test Anal. 2025 Aug;17(8):1443-1456. doi: 10.1002/dta.3849. Epub 2025 Jan 5.
Triptorelin, a synthetic gonadotrophin-releasing hormone (GnRH), is mainly used in the clinical treatment of prostate cancer. The mechanism initially stimulates luteinizing hormone (LH) and testosterone secretion followed by suppression, resulting in a reduction in cancer progression. However, GnRHs are prohibited in doping control because of the indirect surge of LH and testosterone. Therefore, GnRH analog detection and confirmation are enforced by World Anti-Doping Agency (WADA) requirements. The effects of triptorelin on LH and endogenous steroid levels in urine and serum of five prostate cancer patients taking triptorelin for the first time were investigated and compared with leuprorelin. The samples were collected at 0.0 h, 3.0 h, 6.0 h, 1 month, and 3 months later after drug administration. The effect of triptorelin on LH levels was measured using a sandwich enzyme-linked immunoassay (ELISA). Testosterone and endogenous steroid levels were monitored using gas chromatography coupled with mass spectrometry (GC/MS). Triptorelin showed an advantage over leuprorelin on LH and testosterone suppression, which is preferable to use for prostate cancer treatment. In this study, triptorelin (5-10), a unique in vivo metabolite, was found in urine and serum and verified with synthetic triptorelin (5-10). The metabolite was analyzed using liquid chromatography combined with Orbitrap (LC-Orbitrap) and liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF). When triptorelin levels are undetectable, the presence of triptorelin (5-10) in human urine can be used as evidence that triptorelin is being misused in doping control.
曲普瑞林是一种合成的促性腺激素释放激素（GnRH），主要用于前列腺癌的临床治疗。其作用机制最初是刺激黄体生成素（LH）和睾酮分泌，随后是抑制作用，从而减少癌症进展。然而，由于LH和睾酮会间接激增，GnRH在兴奋剂检测中被禁止使用。因此，世界反兴奋剂机构（WADA）要求对GnRH类似物进行检测和确认。研究了曲普瑞林对5例首次服用曲普瑞林的前列腺癌患者尿液和血清中LH及内源性类固醇水平的影响，并与亮丙瑞林进行了比较。在给药后0.0小时、3.0小时、6.0小时、1个月和3个月采集样本。使用夹心酶联免疫吸附测定（ELISA）测量曲普瑞林对LH水平的影响。使用气相色谱-质谱联用（GC/MS）监测睾酮和内源性类固醇水平。曲普瑞林在抑制LH和睾酮方面比亮丙瑞林更具优势，更适合用于前列腺癌治疗。在本研究中，在尿液和血清中发现了曲普瑞林的一种独特的体内代谢产物曲普瑞林（5-10），并与合成的曲普瑞林（5-10）进行了验证。使用液相色谱-静电场轨道阱质谱联用仪（LC-Orbitrap）和液相色谱-离子阱/飞行时间质谱联用仪（LC/MS-IT-TOF）对该代谢产物进行了分析。当曲普瑞林水平检测不到时，人尿中曲普瑞林（5-10）的存在可作为曲普瑞林在兴奋剂检测中被滥用的证据。
