Mechanism and pathways underlying the self-sensitized photodegradation of methotrexate under simulated solar irradiation

Methotrexate, a chemotherapeutic agent, was found to undergo self-sensitized photodegradation in aqueous environments. As the initial concentration increased, methotrexate was able to enhance its own direct photolysis reaction not only in DI but also in natural waters. The methotrexate degradation rate increased through the production of singlet oxygen (O-1(2)), the triplet excited state of methotrexate ((MTX)-M-3*), and the triplet excited state of the pteridine structure ((PT)-P-3*) from the phototransformation byproducts. At low methotrexate concentrations ( < 20 ppb), O-1(2) played an important role, whereas at higher methotrexate concentrations ( > 2000 ppb), the presence of oxygen decreased the overall methotrexate degradation rate by physically quenching (MTX)-M-3* and (PT)-P-3*. The cleavage of the C-N bond resulted in a significant amount of byproducts: pteridine derivatives and N-(4-aminobenzoyl)-L-glutamic acid (yields: 13.5 +/- 0.6% and 32.3 +/- 2.2% for 10 ppm and 500 ppb MTX, respectively). The reactivity of the phototransformation byproducts and the substructures of methotrexate were investigated to help elucidate the proposed self-sensitized pathways. The results indicated that methotrexate as well as compounds containing a pteridine structure will generate pteridine byproducts during photodegradation and (PT)-P-3*. is the primary triplet excited species that can cause self-sensitized photodegradation.