Characterization of piperine metabolites in rats by ultra-high-performance liquid chromatography with electrospray ionization quadruple time-of-flight tandem mass spectrometry.

Abstract

Piperine is a major constituent of Piper nigrum L. and is a naturally bioactive alkaloid. Structural changes in piperine have been shown to result in different biological effects. The present study aims to investigate piperine metabolites in rat plasma, bile, urine, and feces after oral administration. The metabolic pathway of piperine in vivo was investigated using ultra-high-performance liquid chromatography (UHLPC) combined with electrospray ionization quadruple time-of-flight tandem mass spectrometry (QTOF-MS). Piperine metabolites were found and identified by fragmentation patterns and accurate mass measurements. The 12 metabolites detected and identified were divided into three groups: methylenedioxycyclic ring-opening metabolites (M01-M08), methylenedioxycyclic ring-oxidizing metabolites (M09-M11), and piperidine ring-cleavage metabolites (M12). Seven piperine metabolites, including M02, M03, M04, M05, M09, M10 and M11, were reported for the first time in the literature. Results showed that the principal metabolism pathways of piperine in rat were reduction and demethylation after ring-opening, and that UHPLC/QTOF-MS can serve as an important analytical platform to gather the piperine metabolism profile. Copyright © 2017 John Wiley & Sons, Ltd.