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

Anaïs Espinosa,Charles Skarbek,Raphaël Labruère,Sylvie Nélieu,Pascale Lieben,Pierre Benoit

doi:10.1007/s11356-021-15820-3

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 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.

Highlights

Pharmaceuticals and their degradation products are detected in surface waters, wastewater and groundwater at a range of ng/L to mg/L and even in drinking waters (Benotti et al 2009; Mompelat et al 2011)
The kinetics followed a pseudo-first-order with regression coefficients greater than r2 of 0.99, and the constants were determined as 8.8 ± 1.6 10-5 s-1 and 12.4 ± 0.7 10-5 s-1 at pH 7 and 3, respectively (Fig.2 a)
MTX photodegradation can produce a large variety of transformation products (TPs)

Summary

Introduction

Pharmaceuticals and their degradation products are detected in surface waters, wastewater and groundwater at a range of ng/L to mg/L (aus der Beek et al 2016) and even in drinking waters (Benotti et al 2009; Mompelat et al 2011). These occurrences are mainly due to their pharmacokinetics since pharmaceuticals are excreted by patients either as the parent compound (60%-95% - Turci et al 2003) or as metabolites before entering domestic wastewaters. Castiglioni et al (2005) detected nineteen pharmaceuticals in concentrations ranging from 0.5 to 2000 ng/L in Waste Water Treatment Plant (WWTP). Escher and Fenner (2011) have shown that knowledge about TP and metabolites can be relevant for environmental risk assessment because they can be more persistent, more mobile or have a higher toxicity than the parent compound

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Results

Conclusion