Hydroxyaldehyde and formyl photoproducts of protoporphyrin <scp>IX</scp> formed under photodynamic diagnosis and therapy irradiation conditions

Photoproducts of the photosensitizer protoporphyrin IX (PpIX) may have diagnostic and therapeutic relevance in photodynamic diagnosis (PDD) and photodynamic therapy (PDT), as they possess fluorescence and photosensitizing properties and could serve as a complementary dosimetry index alongside photosensitizer photobleaching. Consequently, a detailed characterization of these photoproducts is necessary for exploring their potential application in PDD and PDT. Further, understanding the processes of photobleaching and photoproduct formation will be useful for diagnosis and treatment planning in PDD and PDT. In this study, the formation of four photoproducts previously observed from the irradiation of PpIX-dimethyl ester was extended to investigate their formation from PpIX. PpIX in solution was irradiated at 405 and 635 nm, wavelengths relevant to PDD and PDT, and the formation of the photoproducts was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hydroxyaldehyde and formyl photoproducts, and their isomeric forms, were identified, and their fold increases were evaluated under different irradiation conditions. Although the physicochemical properties of photoproducts depend on the environment, this solution-based study provides fundamental understanding of the photochemical reaction of PpIX and its photoproducts under clinically relevant irradiation conditions and may aid studies aimed at exploiting photoproducts for improved dosimetry and therapeutic outcomes in PDD and PDT.