Structural elucidation of the metabolites of lapachol in rats by liquid chromatography–tandem mass spectrometry

Lapachol is a natural naphthoquinone compound derived from Bignoniaceae (Tabebuia sp.) that possesses a range of significant biological activities. Nine phase I and four phase II metabolites of lapachol in rat bile were firstly elucidated and identified using a sensitive LC-ESI–MSn method. The molecular structures of the metabolites have been presented on the basis of the characteristics of their precursor and product ions, as well as their fragmentation mechanisms and chromatographic retention times. The results indicated that the phase I metabolites were predominantly biotransformed by the hydroxylation, semiquinone hydrogenation at the oxygen position or a side chain rearrangement. The phase II metabolites were identified as the glucuronidated conjugates which showed a characteristic neutral loss of 176 Da. Based on the results of this research, we have proposed the metabolic pathways for lapachol in rats. This work has provided novel information for the in vivo lapachol metabolism which could be used to develop a novel drug candidate, as well as a better understanding of the safety and efficacy of the drug.