HFL Sport Science, Quotient Bioresearch, Newmarket Road, Fordham, CB7 5WW, UK.
Rapid Commun Mass Spectrom. 2013 Oct 30;27(20):2229-38. doi: 10.1002/rcm.6689.
Norethisterone has been used as a successful oral contraceptive in humans for many years. It was recently permitted for use as an oestrus suppressant in racing greyhounds. To monitor the use of norethisterone as part of a routine drug surveillance programme, knowledge of its metabolism was required to enable detection.
Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of norethisterone following oral administration to the greyhound. Metabolites were extracted using solid-phase and liquid-liquid extraction techniques.
Several metabolites were identified, including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17α-ethynyl-5β-estrane-3α,17β-diol, 17α-ethynyl-5α-estrane-3β,17β-diol, three 17α-ethynylestranetriol stereoisomers and two 17α-ethynylestranetetrol stereoisomers. The major metabolites were predominantly excreted as glucuronic acid conjugates and detection of the administration of norethisterone was possible for up to 8 days post-dose using the methods described. The nandrolone metabolites, 19-norepiandrosterone, estranediol and 19-noretiocholanolone, were also identified in the post-administration samples collected up to 8 h after dosing the treated animals.
The urinary metabolites identified in this study have further increased the knowledge of steroid metabolism in the greyhound, providing information to support routine drug testing programmes for greyhound racing.
炔诺酮已被人类用作成功的口服避孕药多年。最近，它被允许作为赛车灰狗的发情抑制剂使用。为了监测炔诺酮作为常规药物监测计划的一部分的使用情况，需要了解其代谢情况以进行检测。
已使用气相色谱/质谱法和选择性衍生化技术来鉴定口服给予灰狗后炔诺酮的尿液代谢物。使用固相和液 - 液萃取技术提取代谢物。
鉴定出几种代谢物，包括还原、单、二和三羟基化甾体。观察到的主要代谢物为 17α-乙炔基-5β-雌烷-3α，17β-二醇、17α-乙炔基-5α-雌烷-3β，17β-二醇、三种 17α-乙炔基雌三醇立体异构体和两种 17α-乙炔基雌四醇立体异构体。主要代谢物主要以葡萄糖醛酸缀合物形式排泄，并且使用描述的方法可以在给药后 8 天内检测到炔诺酮的给药。在给药后收集的样品中还鉴定出了诺龙代谢物 19-去甲雄酮、雌二醇和 19-去甲雄烷酮。
本研究中鉴定出的尿代谢物进一步增加了灰狗中甾体代谢的知识，为灰狗赛车的常规药物测试计划提供了信息支持。
