Semiquantification by ultraviolet (UV) spectroscopy of osimertinib metabolites in mouse, rat, dog, and human hepatocytes

Peak IDProposed StructureProportion (%) of UV Chromatogram (320–330 nm)a
M1Oxidation (+O)<1<11–10<1
M2Dealkylation (-C4H9N)ND<1<1<1
AZ7550Demethylation (-CH2)1–101–101–101–10
M4Oxidation (+O)1–101–101–101–10
M5Oxidation (+O2)<1<1<1ND
AZ5104Demethylation (-CH2)<1<1<1<1
M7Oxidation (+O)NDND<1ND
M8Cysteine-glycine adductND<1ND<1
M9Demethylation (-CH2) + oxidation (+O)1–10<1<1ND
M10Glutathione adduct1–10>101-10<1
M11Acetylation or deamination + glutathione1–101–10NDND
M12Dealkylation (-C4H9N) + glutathione1–10NDNDND
M13Oxidation (+O) + glutathione1–101–10NDND
M14Oxidation (+O) + sulfationNDND<1ND
M15Glutathione adduct<1<1NDND
M16Oxidation (+O) + glucuronidation<1<1NDND
  • a % represents percentage of parent (osimertinib) UV response

  • ND, not detectable by mass spectrometry.