Poon G K, Jarman M, Rowlands M G, Dowsett M, Firth J
Cancer Research Campaign Laboratory, Institute of Cancer Research, Sutton, Surrey, U.K.
J Chromatogr. 1991 Apr 19;565(1-2):75-88. doi: 10.1016/0378-4347(91)80372-j.
A sensitive procedure for studying the metabolism of the steroidal aromatase inhibitor 4-hydroxy-androst-4-ene-3,17-dione (4OHA) was developed based on enzyme hydrolysis, liquid-liquid extraction and reversed-phase liquid chromatography coupled with a mass spectrometer (LC-MS) using a thermospray interface. Seven metabolites were identified from the hydrolysed urine samples together with the parent drug. The major routes of metabolism were via dehydrogenation, reduction of the ketone functional groups, reduction at the C-4-C-5 double bond and hydroxylation at the C-5 position. Confirmation of the identity of 4OHA and its metabolites isolated from female patients' urine samples was accomplished by comparison of the retention times of their corresponding synthetic standards on LC-MS. We have demonstrated that this technique is particularly suitable for studying the metabolism of steroidal drugs.
基于酶水解、液-液萃取以及使用热喷雾接口的反相液相色谱与质谱联用（LC-MS）技术，开发了一种用于研究甾体芳香酶抑制剂4-羟基雄甾-4-烯-3,17-二酮（4OHA）代谢的灵敏方法。从水解后的尿液样本中鉴定出了七种代谢物以及母体药物。主要代谢途径包括脱氢、酮官能团的还原、C-4-C-5双键处的还原以及C-5位的羟基化。通过比较4OHA及其从女性患者尿液样本中分离出的代谢物与相应合成标准品在LC-MS上的保留时间，确认了它们的身份。我们已经证明该技术特别适用于研究甾体药物的代谢。
