Differences and Similarities in the Metabolism of Erlotinib across various Species: An Analysis by Liquid Chromatography - Tandem Mass Spectrometry

Abstract

Erlotinib is an inhibitor of the epidermal growth factor receptor (EGFR), primarily used to treat non-small cell lung cancer (NSCLC) or pancreatic cancer. The main objective of the present study was to identify differences and similarities in the metabolism of erlotinib across various species and to identify new phase I metabolites. Metabolic characteristics of erlotinib were investigated in liver microsomes of human, mice, rat, dog, hamster, and S9-fraction of mice by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 19 phase I metabolites were detected in human liver microsomes; whereas, 12 metabolites in each of mice-, rat- liver microsomes and S9-fraction of mice; 10 in dog liver microsomes and 7 in hamster liver microsomes were detected. Out of these 19 metabolites, 8 metabolites were newly found including 1- novel metabolite (M23) which was identified with its putative structure in human liver microsomes. All phase I metabolites reported in healthy human volunteers were identified in human liver microsomes. Similar metabolic behavior had shown by liver microsomes of mice, rat, and S9-fraction of mice. Metabolites M6, M13, M14, M16, M22, and M25 were found in all tested species. These differences and similarities in the metabolism of erlotinib confirmed the role of CYP 450 enzymes and their distinct activity across various species.