a Department of Pharmacology and PharmacoGenomics Research Center , Inje University College of Medicine , Busan , Korea.
b Korea Institute of Toxicology , Yuseong-gu, Daejeon , Korea.
J Toxicol Environ Health A. 2018;81(12):481-492. doi: 10.1080/15287394.2018.1460783. Epub 2018 Apr 11.
Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively utilized in treatment of life-threatening ventricular and supraventricular arrhythmias. However, amiodarone also produces adverse side effects including liver injury due to its metabolites rather than parent drug. The purpose of the present study was to identify metabolites of amiodarone in the plasma and urine of rats administered the drug by using an untargeted metabolomics approach. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and results subjected to multivariate data analysis. A total of 49 amiodarone metabolites were identified and their structures were characterized by tandem mass spectrometry. Amiodarone metabolites are presumed to be generated via five major types of metabolic reactions including N-desethylation, hydroxylation, carboxylation (oxo/hydroxylation), de-iodination, and glucuronidation. Data demonstrated that an untargeted metabolomics approach appeared to be a reliable tool for identifying unknown metabolites in a complex biological matrix.
胺碘酮是一种苯并呋喃类 III 类抗心律失常药物，广泛用于治疗危及生命的室性和室上性心律失常。然而，胺碘酮的代谢物也会产生不良反应，包括肝损伤，而不是母体药物。本研究旨在采用非靶向代谢组学方法鉴定给予胺碘酮的大鼠血浆和尿液中的胺碘酮代谢物。采用超高效液相色谱-电喷雾电离四极杆飞行时间质谱（UPLC-ESI-QTOFMS）对药物代谢物进行分析，并对结果进行多变量数据分析。共鉴定出 49 种胺碘酮代谢物，并通过串联质谱对其结构进行了表征。胺碘酮代谢物可能通过 N-去乙基化、羟化、羧化（氧化/羟化）、去碘化和葡萄糖醛酸化等五种主要代谢反应生成。研究数据表明，非靶向代谢组学方法似乎是鉴定复杂生物基质中未知代谢物的可靠工具。
