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本瑞克斯的新陈代谢得到了电化学-质谱仪的补充

Valentin Göldner¹, Uwe Karst¹

¹Institute of Inorganic and Analytical Chemistry, University of Münster, Corrensstraße 48, 48149 Münster, Germany; International Graduate School for Battery Chemistry, Characterization, Analysis, Recycling and Application (BACCARA), University of Münster, Corrensstraße 40, 48149 Münster, Germany.

Journal of pharmaceutical and biomedical analysis

|August 5, 2023

概括

糖尿病药物Benfluorex与心脏和肺部问题有关. 它的代谢物norfenfluramine是通过电化学识别的,这表明这种方法可以更早地预测药物安全风险.

科学领域:

药理学药理学是指药理学的学科.
分析化学分析化学
毒理学毒理学毒理学

背景情况:

用于治疗2型糖尿病和代谢综合征的Benfluorex与膜心脏病和肺动脉高血压有关.
这些不良药物反应类似于芬拉胺的副作用,与其代谢物诺芬拉胺有关.
尽管norfenfluramine是这两种药物的代谢物,但benfluorex在市场上存在的时间比fenfluramine更长.

研究的目的:

模拟benfluorex的新陈代谢并识别其转化产品.
评估电化学方法对快速药物代谢物查和安全性评估的有用性.

主要方法:

电化学和质谱学的在线连接,以模拟benfluorex代谢.
液体染色学和高分辨率联质谱学用于表征转化产品.

主要成果:

诺芬拉胺被确定为benfluorex的主要电化学转化产物.
电化学代谢模拟成功识别了一种已知的有毒代谢产物.

结论:

使用电化学质谱的快速代谢物查可以早期预测潜在的不良药物反应.
电化学代谢模拟对于及时评估药物安全性是有价值的,有可能防止以后的市场撤回.

关键词:

本弗洛雷克斯 (Benfluorex) 是一种电化学电化学电化学质谱测量质量谱测量代谢过程中的代谢.诺芬黄胺是一种诺芬黄胺.

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