Rapid multi-component detection of fluorinated drug metabolites in whole urine from a ‘cassette’ dose study using high resolution 19F NMR spectroscopy

O. Corcoran, J. Nicholson, I. Wilson
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引用次数: 8

Abstract

High resolution 19F NMR spectroscopy has been successfully applied to the analysis of drug metabolites in whole rat urine from a ‘cassette’ dose study of 6 fluorinated test compounds dosed at 10 mg kg–1 per compound. A total of 21 compound-related molecules were rapidly detected in the 0–8 h urine samples. The metabolic fate of the compounds after cassette administration appeared to be the same as when the compounds were dosed individually. 19F NMR may thus enable metabolism to be estimated for several compounds simultaneously, with minimal sample preparation, and without interference from endogenous molecules in the biofluid. This analytical approach may therefore be of value at the drug discovery stage in the development of ‘high throughput’ in vivo metabolic screens.
使用高分辨率19F核磁共振波谱法从“盒式”剂量研究中快速检测全尿中氟化药物代谢物的多组分
高分辨率19F核磁共振波谱已成功应用于对6种氟化试验化合物的“盒式”剂量研究中全鼠尿液中的药物代谢物的分析,每种化合物的剂量为10 mg kg-1。在0-8 h尿样中快速检测到21种化合物相关分子。盒式给药后化合物的代谢命运似乎与单独给药时相同。因此,19F NMR可以同时估计几种化合物的代谢,只需最少的样品制备,并且不受生物流体中内源性分子的干扰。因此,这种分析方法可能在开发“高通量”体内代谢筛选的药物发现阶段具有价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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