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定量 NMR 研究电化学生成的反应性药物代谢物的降解。

Understanding the degradation of electrochemically-generated reactive drug metabolites by quantitative NMR.

机构信息

LUNAM Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230, 2 rue de la Houssinière, BP 92208, F-44322 Nantes cedex 3, France.

出版信息

Talanta. 2013 Nov 15;116:554-8. doi: 10.1016/j.talanta.2013.07.026. Epub 2013 Jul 19.

DOI:10.1016/j.talanta.2013.07.026
PMID:24148444
Abstract

Phenacetin is known to be metabolized to N-AcetylParaBenzoQuinoneImine (NAPQI), which is a common metabolite of paracetamol (also called acetaminophen or APAP). The electrochemical conversion of APAP to NAPQI was shown in 1989 by Getek and co-workers, thus demonstrating the capacity of electrochemistry to mimic the formation of NAPQI from APAP as well as from phenacetin. This study focuses on a preparative electrochemical electrolysis associated with quantitative (1)H NMR. On one hand, this method is able to synthesize reactive metabolites in sufficient concentrations and amounts for NMR analysis. On the other hand, NMR allows the simultaneous detection and quantification of all chemical species, in contrast to mass spectrometry. The combination of electrochemistry with quantitative NMR is thus presented as a relevant method for elucidating the degradation of reactive metabolites and may be considered a valuable complementary tool to EC-MS.

摘要

非那西汀已知可代谢为 N-乙酰对苯醌亚胺(NAPQI),这是对乙酰氨基酚(也称为扑热息痛或 APAP)的常见代谢物。Getek 及其同事于 1989 年证明了 APAP 的电化学转化为 NAPQI,从而证明了电化学模拟从 APAP 以及从非那西汀形成 NAPQI 的能力。本研究侧重于与定量(1)H NMR 相关的制备电化学电解。一方面,该方法能够以足够的浓度和数量合成反应性代谢物,用于 NMR 分析。另一方面,与质谱相比,NMR 允许同时检测和定量所有化学物质。因此,将电化学与定量 NMR 相结合被提出作为阐明反应性代谢物降解的相关方法,并且可以被认为是 EC-MS 的有价值的补充工具。

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