Photodegradation of methotrexate in aqueous solution: degradation kinetics and identification of transformation products

Abstract

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 identi ed by UHPLC-MS/MS, using both the positive and negative modes. Among the eleven proposed structures, ve were described as methotrexate TPs for the rst time. The TPs result from N-demethylation, glutamic acid oxidation and C-N cleavage, all of them leading to further degraded photoproducts presenting modi ed or lost glutamic acid part. This was made possible thanks to the negative mode, which allowed the exploration of the glutamic acid moiety modi cations. Cytotoxicity assessment on A549 cancer cells demonstrated that all photoproducts formed at pH 7 were less toxic than the parent compound.

Statistical Analysis of Methotrexate Degradation by UV-C Photolysis and UV-C/TiO2 Photocatalysis

“…After 120 min of reaction, a maximum of 65.73% was reached at a pH of 3.5 (Figure 2). Similar results were obtained by Espinosa et al [31], who achieved a 73% degradation of MTX at a pH of 3 and radiation with a wavelength of 254 nm. Remarkably, photocatalytic kinetic constants were lower than those calculated for the photolytic process, with values for experiments when H 2 O 2 was added of 0.016 min −1 , 0.005 min −1 , and 0.008 min −1 for initial pH values of 3.5, 7, and 9.5, respectively.…”

Evaluation of Potential Ecotoxicity of Cefepime Phototransformation Products

“…Similarly, the toxicity assessment of a mixture of compounds after irradiation was carried out by Cantalupi et al [10]. According to our analysis, the toxicity of photodegradation products such as methotrexate [15], ketoprofen [16,17], sertaline [11], citalopram [18] and verapamil [19] have been studied so far. Our study is the first to evaluate the ecotoxicity of cefepime.…”

Methotrexate degradation in artificial wastewater using non-thermal pencil plasma jet

“…The second pathway involves cleavage of C-C and C-N bonds with high energy atoms and molecules in the presence of UV radiation and heat, resulting in compounds such as N-(4-Aminobenzoyl)-L-glutamic acid, 4-Aminobenzamide, 2,4-Diaminopteridine, and 2-Aminohexanedioic acid, etc. as shown in figure 6 (2,7,8,19,20). Further mineralization of these compounds (product from both pathway) generated NO 2 ˉ ions, NO 3 ˉ ions in aqueous phase as well as release CO 2 and H 2 O in gas and vapor phase as shown in figure 6.…”

“…Some of these anticancer drugs are cytotoxic. Therefore, their presence in wastewater is a threat to aquatic ecosystems (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…Therefore, the degradation of MTX in water becomes important to protect the environment from its adverse effects. (2,7,8,19,20).…”