Identification Of A Hydroxylamine Glucuronide Metabolite Of An Oral Hypoglycemic Agent
DRUG METABOLISM AND DISPOSITION(2004)
摘要
Glucuronides of piperazine hydroxylamines are rarely reported in the literature, and even more rarely are their structures unambiguously identified. One major metabolite was detected by liquid chromatography/ mass spectrometry-radioactivity in urine from monkeys treated with the aryl piperazine oral hypoglycemic agent 9-[(1S,2R)2- fluoro-1-methylpropyl]-2-methoxy-6-(1-piperazinyl) purine hydrochloride ( 1). The mass spectrum of this metabolite indicated that it was both monooxygenated and glucuronidated on the piperazine ring. Possible structures included the N- or O-glucuronic acid conjugates of a carbinolamine, hydroxylamine, or N- oxide. Treatment with beta-glucuronidase gave a monooxygenated derivative of the parent compound. H-1 NMR analysis of either the glucuronic acid conjugate or the monooxygenated product provided insufficient evidence to unambiguously determine their structures. Incubation of 1 with pig liver microsomes resulted in formation of the same monooxygenated derivative derived from beta-glucuronidase treatment of the glucuronide metabolite. This in vitro system was used to generate sufficient material for analysis by C-13 NMR, and the metabolite was identified as a hydroxylamine derivative 2. Incubation of the hydroxylamine with monkey liver microsomes and uridine diphospho-5'-glucuronic acid gave the same glucuronic acid conjugate as that observed in monkey urine. C-13 NMR analysis of this biosynthetic product led to its unequivocal structure assignment as the O-glucuronic acid conjugate of the hydroxylamine 3.
更多查看译文
关键词
hydroxylamine glucuronide metabolite
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要