Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Analytical Science and National Doping Test Institute (ASNDTI), Mahidol University, Bangkok 10400, Thailand.
Molecules. 2023 Jun 6;28(12):4572. doi: 10.3390/molecules28124572.
Triptorelin and leuprorelin are synthetic gonadotrophin-releasing hormones (GnRH) that are on the World Anti-Doping Agency (WADA) list of prohibited substances. To investigate the possible in vivo metabolites of triptorelin and leuprorelin in humans compared to previously reported in vitro metabolites, excreted urine from five patients treated with either triptorelin or leuprorelin was analyzed by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF). The addition of dimethyl sulfoxide (DMSO) to the mobile phase was found to enhance the detection sensitivity of certain GnRH analogs. The method was validated, and the limit of detection (LOD) was found at 0.02-0.08 ng/mL. Using this method, a novel new metabolite of triptorelin was discovered in the urine of all subjects up to 1 month after triptorelin administration, but it was not observed in the urine of subjects before drug administration. The limit of detection was estimated to be 0.05 ng/mL. The structure of the metabolite, triptorelin (5-10), is proposed from bottom-up mass spectrometry analysis. The discovery of in vivo triptorelin (5-10) can possibly be used as supporting evidence of triptorelin misuse in athletes.
曲普瑞林和亮丙瑞林是合成的促性腺激素释放激素（GnRH），被世界反兴奋剂机构（WADA）列入禁用物质清单。为了研究与先前报道的体外代谢物相比，曲普瑞林和亮丙瑞林在人体内的可能的体内代谢物，对接受曲普瑞林或亮丙瑞林治疗的五名患者的排泄尿液进行了分析，方法是通过液相色谱-离子阱/飞行时间质谱联用（LC/MS-IT-TOF）。发现向流动相中添加二甲基亚砜（DMSO）可以增强某些 GnRH 类似物的检测灵敏度。对该方法进行了验证，检测限（LOD）为 0.02-0.08ng/mL。使用该方法，在曲普瑞林给药后 1 个月内，所有受试者的尿液中均发现了曲普瑞林的一种新的新型代谢物，但在受试者给药前的尿液中未观察到。代谢物的结构，推测为三普瑞林（5-10），通过自上而下的质谱分析得出。体内曲普瑞林（5-10）的发现可能可作为运动员曲普瑞林滥用的支持证据。
