Investigation of metabolic profiling of leelamine in vitro and in vivo by LC‐MS/MS

Abstract

Leelamine is a diterpene compound found in the bark of pine trees that is generating considerable interest owing to its potent anticancer properties. The present study aimed to investigate the metabolic profile of leelamine in human liver microsomes (HLMs) and mice using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). We found that leelamine undergoes only Phase I metabolism, which generates one metabolite that is mono‐hydroxylated at the C9 carbon of the octahydrophenanthrene ring (M1) both in vitro and in vivo. The structure and metabolic pathway of M1 were determined from the MSn fragmentation obtained by collision‐induced dissociation using LC‐MS/MS in HLMs. Cytochrome p450 (CYP) 2D6 was found to be the dominant CYP enzyme involved in the biotransformation of leelamine to its hydroxylated metabolite while CYP2C19, CYP1A1, and CYP3A4 contributed to some extent. Moreover, further investigation of the in vivo metabolism of leelamine in mice using urinary and fecal analysis detected only one metabolite, M1, in the urine but none in the feces. In conclusion, leelamine was metabolized to mono‐hydroxyl metabolite by CYP2D6 and mainly excreted in the urine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.