Identification and characterization of amiodarone metabolites in rats using UPLC-ESI-QTOFMS-based untargeted metabolomics approach.
J Toxicol Environ Health A
; 81(12): 481-492, 2018.
Article
en En
| MEDLINE
| ID: mdl-29641932
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Amiodarona
/
Antiarrítmicos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Toxicol Environ Health A
Asunto de la revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Año:
2018
Tipo del documento:
Article