LAUSR

Abemaciclib is approved by US Food and Drug Administration in 2015 to have an advanced treatment for metastatic breast cancer. Identification and characterization of limited numbers of abemaciclib metabolites have been reported in the literature. Therefore, the current study focused on the investigation of in vitro and in vivo metabolic fate of abemaciclib using high resolution mass spectrometry. Initially, vulnerable site of metabolism were predicted by Xenosite web predictor tool. Later, in vitro metabolites were identified from pooled rat liver microsomes, rat S9 fractions and human liver microsomes. Finally, in vivo metabolites have been detected in plasma, urine and feces matrix of male Sprague-Dawley rats. A total of 12 putative metabolites (11 phase I and 1 phase II) of abemaciclib and their metabolic pathways were proposed by considering accurate mass, mass fragmentation pattern, nitrogen rule and ring double bonds of detected metabolites. Abemaciclib was metabolized via hydroxylation, N-oxidation, N-dealkylation, oxidative deamination followed by reduction and sulfate conjugation. In the human liver microsomes, maximum numbers of metabolites (11 metabolites) were observed and from which M7, M8, M9 and M11 were human specific.