Conclusions
Humans have a relatively low capability for metabolizing ibrutinib. Compared with rat, dog had closer metabolic profiles to humans and would be more suitable for toxicity studies. This study provides more valuable information with respect to the in vitro disposition of ibrutinib.
Methods
Ibrutinib was incubated with hepatocytes at 37°C for 2 h, after which the samples were analyzed using ultrahigh-performance liquid chromatography with diode-array detection and Q-Exactive Orbitrap tandem mass spectrometry (UHPLC/DAD-Q-Exactive-Orbitrap-MS). The acquired data were processed using MetWorks™ software.
Results
A total of 20 metabolites were structurally identified by their MS and MS2 data. M1 and M5 were unambiguously identified using authentic standards. The biotransformation of ibrutinib involved hydroxylation, hydration, oxygenation, epoxide hydrolysis, dehydrogenation, dealkylation and GSH conjugation. Conclusions: Humans have a relatively low capability for metabolizing ibrutinib. Compared with rat, dog had closer metabolic profiles to humans and would be more suitable for toxicity studies. This study provides more valuable information with respect to the in vitro disposition of ibrutinib.