Conclusions
The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.
Methods
The metabolites were generated by individually incubating daporinad (10 μM) with liver microsomes at 37°C for 60 min. The metabolites were identified by ultra-high-performance liquid chromatography/quadrupole-orbitrap mass spectrometry (UPLC/Q-Orbitrap-MS) using electrospray ionization in positive ion mode. They were deduced by accurate MS and MS/MS data.
Results
In total, 16 metabolites were found and their identities were characterized. In rat, dog and human, they were minor; in monkey, M11 was the most abundant. Daporinad was metabolized mainly through N-dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. There was no human-specific metabolite. Conclusions: The current study provided an overview of the metabolism of daporinad, which is helpful in predicting in vivo metabolites and in selecting animal species for toxicology studies.