Comprehensive characterization of the in vitro and in vivo metabolites of limonin in human samples using LC-Q-TOF/MS

Limonin is a bitter triterpenoid dilactone in the genus Citrus with potential medicinal value. In this study, the metabolism of limonin in human was characterized by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). A total of 7 metabolites were identified from human samples. Among them, 3 metabolites of M1, M2 and M4 were detected in urine and feces, and the others were found in intestinal bacteria sample. Notably, M1 and M3 were chemically synthesized, of which the structures were further confirmed by NMR spectra data. The metabolism of limonin involved three major pathways, namely, reduction, hydrolysis and methylation. The reduction and hydrolysis were commonly observed in ring D of limonin. The metabolites showed decomposition in ring A. This study provides data for the metabolism of limonin in humans, and will contribute to explain its biological activity.