Characterization of stable and reactive metabolites of piperine formed on incubation with human liver microsomes

AbstractBlack pepper, though commonly employed as a spice, has many medicinal properties. It consists of volatile oils, alkaloids, pungent resins,etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose, and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, β‐unsaturated carbonyl group (Michael acceptor) and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed onin vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz., glutathione (GSH) and N ‐acetylcysteine (NAC). The samples were analysed by ultra‐high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC‐HRMS) using Thermo ScientificTM Q Exactive PlusTM Orbitrap. Full scan MS followed by data ‐dependent MS2 (Full MS ‐ddMS2) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a ‐c, M2a‐b, M3a‐c and M4a‐b) were detected. Their formation involved removal of carbon (3, M1a‐c), hydroxylation (2, M2a‐b), hydroxylation with hydrogenation (3, M3a‐c), and dehydrogenation (2, M4a‐b). Out of these me...
Source: Journal of Mass Spectrometry - Category: Chemistry Authors: Tags: RESEARCH ARTICLE Source Type: research