Mareck U, Sigmund G, Opfermann G, Geyer H, Thevis M, Schänzer W
Institute of Biochemistry, German Sport University Cologne, Carl-Diem-Weg 6, 50933 Cologne, Germany.
Rapid Commun Mass Spectrom. 2005;19(24):3689-93. doi: 10.1002/rcm.2239.
Letrozole (1-(bis-(4-cyanophenyl)methyl)-1,2,4-triazole) is used therapeutically as a non-steroidal aromatase inhibitor (Femara) to treat hormone-sensitive breast cancer in postmenopausal women. For doping purposes it may be used to counteract the adverse effects of an extensive abuse of anabolic androgenic steroids (gynaecomastia) and to increase the testosterone concentration by stimulation of the testosterone biosynthesis. The use of aromatase inhibitors has been prohibited by IOC/WADA regulations for male and female athletes since September 2001 and January 2005, respectively. Spot urine samples from women suffering from metastatic breast cancer and being treated with letrozole were collected and analysed to develop/optimise the detection system for metabolites of letrozole to allow the identification of athletes who do not comply with the internationally prohibited use of this cancer drug. The assay was based on gas chromatography/mass spectrometry (GC/MS) and the main metabolite of letrozole (bis-4-cyanophenylmethanol) was identified by comparison of its mass spectrum and retention time with that of a bis-4-cyanophenylmethanol reference. The full-scan spectrum, diagnostic ions and a validation of the method for the analysis of bis-4-cyanophenylmethanol are presented.
来曲唑（1-（双-（4-氰基苯基）甲基）-1,2,4-三唑）作为一种非甾体芳香酶抑制剂（商品名：芙瑞）在治疗上用于绝经后女性的激素敏感性乳腺癌。出于兴奋剂使用目的，它可能被用于对抗大量滥用合成代谢雄激素类固醇所产生的不良影响（男性乳房发育），并通过刺激睾酮生物合成来提高睾酮浓度。自2001年9月和2005年1月起，国际奥委会/世界反兴奋剂机构的规定分别禁止男女运动员使用芳香酶抑制剂。收集并分析了正在接受来曲唑治疗的转移性乳腺癌女性的尿样，以开发/优化来曲唑代谢物的检测系统，从而能够识别违规使用这种抗癌药物的运动员。该检测基于气相色谱/质谱联用（GC/MS）技术，通过将其质谱图和保留时间与双-4-氰基苯基甲醇对照品进行比较，鉴定出来曲唑的主要代谢物（双-4-氰基苯基甲醇）。文中给出了全扫描谱图、诊断离子以及双-4-氰基苯基甲醇分析方法的验证结果。
