Journal
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
Volume 29, Issue 4, Pages 6060-6071Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s11356-021-15820-3
Keywords
Methotrexate; Anticancer drug; Photo irradiation; Transformation products; Structural identification; Degradation pathway; Cytotoxicity
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Funding
- French National Agency for Research [ANR-16-CE34-000101]
- INRAE (Environment and Agronomy division)
- French ministry of Agriculture and Food
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This study focused on the photodegradation of methotrexate under two irradiation conditions, with experiments conducted at different pH levels to produce a variety of transformation products. The degradation kinetics were contrasted according to pH and irradiation wavelength, with identification of transformation products using UHPLC-MS/MS. The study found that the photoproducts formed at pH 7 were less toxic than the parent compound when assessed for cytotoxicity on A549 cancer cells.
Methotrexate is an antineoplastic folate analog of high environmental concern, due to its low biodegradability and toxicological properties. This study focused on its photodegradation under two irradiation conditions, aiming to be representative of environment (300-450 nm) and drinking water treatment (254 nm). The photodegradation experiments were conducted at two pH, to vary the methotrexate ionization state and to produce a large variety of transformation products (TPs). The degradation kinetics determined through LC-UV monitoring were contrasted according to pH and irradiation wavelength. However, the quantum yields were independent of ionization state at 254 nm and the changes in kinetics at higher wavelengths were attributed to a change in the degradation mechanism. The TPs formed during the reactions were identified by UHPLC-MS/MS, using both the positive and negative modes. Among the eleven proposed structures, five were described as methotrexate TPs for the first time. The TPs result from N-demethylation, glutamic acid oxidation, and C-N cleavage, all of them leading to further degraded photoproducts presenting modified or lost glutamic acid part. This was made possible thanks to the negative mode, which allowed the exploration of the glutamic acid moiety modifications. Cytotoxicity assessment on A549 cancer cells demonstrated that all photoproducts formed at pH 7 were less toxic than the parent compound.
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