Beumer Jan-Hendrik, Hillebrand Michel J X, Pluim Dick, Rosing Hilde, Foley Karen, Yule S Murray, Schellens Jan H M, Beijnen Jos H
Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Invest New Drugs. 2005 Aug;23(4):317-30. doi: 10.1007/s10637-005-1440-4.
Indisulam is a new anticancer drug with a unique mechanism of action, arresting the cell cycle at the G1/S transition. The major excretory pathway of indisulam is via the urine, accounting for 63% of the radioactive dose ([(14)C]indisulam) administered in a human mass balance study. Radiochromatographic profiling of urine samples resulted in the detection of several radioactive peaks. The purpose of the present investigation was to elucidate the chemical structures of these observed indisulam metabolites. We collected fractions after chromatographic separation of the urine samples. These fractions were analysed using tandem mass spectrometry. We propose the chemical structure of 15 indisulam metabolites in urine. The metabolism of indisulam is very complex, consisting of oxidative dechlorination, hydroxylation, hydrolysis, acetylation, sulphation and glucuronidation. The clinical relevance of the observed indisulam metabolites needs further investigation.
因迪舒兰是一种具有独特作用机制的新型抗癌药物，可在G1/S期转换点阻滞细胞周期。因迪舒兰的主要排泄途径是通过尿液，在一项人体质量平衡研究中，尿液排泄量占给药放射性剂量（[14C]因迪舒兰）的63%。对尿液样本进行放射色谱分析，检测到多个放射性峰。本研究的目的是阐明这些观察到的因迪舒兰代谢物的化学结构。我们在对尿液样本进行色谱分离后收集了馏分。使用串联质谱对这些馏分进行分析。我们提出了尿液中15种因迪舒兰代谢物的化学结构。因迪舒兰的代谢非常复杂，包括氧化脱氯、羟基化、水解、乙酰化、硫酸化和葡萄糖醛酸化。观察到的因迪舒兰代谢物的临床相关性需要进一步研究。
