Honokiol Metabolites Study in Rat Kidney Employing UHPLC-Q-TOF/MS and 13C Stable Isotope Labeling

Kidneys are an important organ since they make a significant contribution to the metabolism and excretion of drugs in vivo. The aim of this study was to identity and tentatively elucidate honokiol metabolites in the rat kidney, after healthy rats were exposed to a 1:1 mixture of labeled 13C-honokiol and unlabeled honokiol, by ultra high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer platform. This platform is well known for its fast acquisition speed, superior sensitivity, high resolution, and excellent mass accuracy. Finally, a total of 19 metabolites belonging to phase II metabolites were identified tentatively by exact mass, and the fragmentation spectra of four metabolites are reported for the first reported time. Our results indicated that honokiol was metabolized via phase II biotransformation including sulfation, acetylation, glucuronidation and amino acid conjugation in rat kidney tissues. This is the first study focused on the honokiol biotransformation in the tissue of kidney, providing important details for a comprehensive standing of the metabolites of honokiol.