Identification of metabolites of adonifoline, a hepatotoxic pyrrolizidine alkaloid, by liquid chromatography/tandem and high-resolution mass spectrometry

Abstract

Hepatotoxic pyrrolizidine alkaloid (HPA)-containing plants have always been a threat to human and livestock health worldwide. Adonifoline, a main HPA in <i>Senecio scandens</i> Buch.-Ham. ex D. Don (Qianli guang), was used officially as an infusion in cases of oral and pharyngeal infections in China. In this study <i>in vivo</i> metabolism of adonifoline was studied for the first time by identifying the metabolites of adonifoline present in bile, urine and feces of rats using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MSⁿ) (ion trap) as well as liquid chromatography/electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS) (quadrupole-time of flight). In total 19 metabolites were identified and, among them, retronecine-<i>N</i>-oxides were confirmed by matching their fragmentation patterns with their fully characterized synthetic compounds. These metabolites are all involved in both phase I and phase II metabolic processes and the principal <i>in vivo</i> metabolism pathways of adonifoline were proposed.