Semiquantification by ultraviolet (UV) spectroscopy of osimertinib metabolites in mouse, rat, dog, and human hepatocytes
| Peak ID | Proposed Structure | Proportion (%) of UV Chromatogram (320–330 nm)a | |||
|---|---|---|---|---|---|
| Mouse | Rat | Dog | Human | ||
| M1 | Oxidation (+O) | <1 | <1 | 1–10 | <1 |
| M2 | Dealkylation (-C4H9N) | ND | <1 | <1 | <1 |
| AZ7550 | Demethylation (-CH2) | 1–10 | 1–10 | 1–10 | 1–10 |
| M4 | Oxidation (+O) | 1–10 | 1–10 | 1–10 | 1–10 |
| M5 | Oxidation (+O2) | <1 | <1 | <1 | ND |
| AZ5104 | Demethylation (-CH2) | <1 | <1 | <1 | <1 |
| M7 | Oxidation (+O) | ND | ND | <1 | ND |
| M8 | Cysteine-glycine adduct | ND | <1 | ND | <1 |
| M9 | Demethylation (-CH2) + oxidation (+O) | 1–10 | <1 | <1 | ND |
| M10 | Glutathione adduct | 1–10 | >10 | 1-10 | <1 |
| M11 | Acetylation or deamination + glutathione | 1–10 | 1–10 | ND | ND |
| M12 | Dealkylation (-C4H9N) + glutathione | 1–10 | ND | ND | ND |
| M13 | Oxidation (+O) + glutathione | 1–10 | 1–10 | ND | ND |
| M14 | Oxidation (+O) + sulfation | ND | ND | <1 | ND |
| M15 | Glutathione adduct | <1 | <1 | ND | ND |
| M16 | Oxidation (+O) + glucuronidation | <1 | <1 | ND | ND |
↵a % represents percentage of parent (osimertinib) UV response
ND, not detectable by mass spectrometry.