Metabolite Profiling of Naringin in Rat Urine and Feces Using Stable Isotope-Labeling-Based Liquid Chromatography-Mass Spectrometry

Naringin has been documented to possess various bioactivities. Due to thorny endogenous interferences, the metabolism pathways of naringin and exact amounts of derived phenolic catabolites have not been definitely assigned. In this work, stable isotope-labeling-based liquid chromatography-mass spectrometry methods were developed to eliminate the endogenous interferences. [2′,3′,5′,6′-D4]-naringin was orally administrated to rats. Urine and feces samples were collected and then analyzed with ultrahigh-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS). A total of 21 flavonoid metabolites and 11 phenolic catabolites were screened. The metabolism and catabolism pathways were proposed. Furthermore, deuterated naringin and its main metabolites were determined with rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QqQ-MS/MS). The overall recovery of ingested deuterated naringin was calculated as 56.9% without endogenous interferences. The obtained results provide essential information for further pharmacological studies of naringin.