Analysis of Photoinduced Degradation of Afatinib: Associated Photochemical and Photobiological Reactions

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinoma (NSCLC) accounting for most cases. Many patients are diagnosed at advanced stages, where conventional therapies are no longer viable. The discovery of mutations in the epidermal growth factor receptor (EGFR) has enabled the development of targeted therapies, including oral EGFR tyrosine kinase inhibitors (TKIs). Among these, Afatinib stands out as an irreversible, highly selective EGFR inhibitor approved for first-line treatment of NSCLC. This study investigates the photochemical and photophysical properties of Afatinib (AFT) under UVA irradiation to evaluate its photostability, along with its degradation kinetics. Steady-state absorption and emission spectra were recorded in solvents of varying polarity to distinguish between locally excited (LE) and intramolecular charge transfer (ICT) states. Excited-state energies were estimated, and fluorescence lifetimes measured to assess solvent-dependent behavior. AFT solutions in toluene and acetonitrile were irradiated for different times. The resulting photoproducts were analyzed by HPLC and ¹H-NMR spectroscopy. The NMR spectra showed new peaks in the aromatic region and changes in aliphatic signals, indicating structural transformations even at short exposure. These results confirm Afatinib’s photoactive character. Binding studies with human serum albumin (HSA) were also performed to explore interactions in biological environments. Although laser flash photolysis (LFP) experiments did not reveal triplet excited-state signals or singlet oxygen (¹O₂) formation, the data support the hypothesis that Afatinib undergoes mainly Type I phototoxic mechanisms, driven by electron or hydrogen transfer from the singlet excited state. Overall, these findings provide insight into the photochemical behavior of AFT, with implications for its stability, formulation, and clinical safety profile.