Evaluation of uptake of the cytostatic methotrexate in Elliptio complanata mussels by LC–MS/MS

Sylvie Poirier Larabie,Isabelle St-Jean,Christian Gagnon,Grégoire Leclair,François Gagné,Christine Kleinert,Martin Jutras

doi:10.1007/s11356-022-19064-7

Abstract

Aquatic organisms are continuously exposed to emerging contaminants coming from urban effluents of wastewater treatment plants. The contamination of surface water by those effluents poses a number of environmental risks, and pharmaceuticals are part of this class of effluent contaminants. Various classes of pharmaceuticals are not treated by wastewater treatment plants and anticancer drugs are part of them. The chemotherapy drug methotrexate (MTX) is an emerging contaminant and its growing use with the increase in cancer cases worldwide raises potential risk to aquatic organisms exposed to effluent discharges. However, chemical analyses in exposed freshwater aquatic organisms for ecotoxicological studies are rarely available and no studies have been done yet to accompany ecotoxicological data of exposed filter-feeding organisms. The purpose of this study was to develop a specific and sensitive analytical LC–MS/MS method for the quantification of methotrexate uptake in mussels exposed at different concentrations of the drug. A solid/liquid extraction followed by solid phase extraction (SPE) using an MCX phase purification scheme was optimized. The optimal recovery of 65% and matrix effect of 38% allowed to achieve a limit of quantification of 0.25 ng g−1, with an accuracy of 99–106%, a precision of no more than 3% RSD, and linearity ranging from 0.25 to 25 ng g−1. This methodology was tested with mussels exposed for 96 h at different concentrations (4 to 100 µg L−1) of MTX. The data revealed tissue uptake at concentrations ranging from 0 to 2.53 ng g−1. This suggests that this drug has low uptake potential and this methodology could be used to examine tissue levels of this drug in organisms continuously exposed to urban pollution.

Highlights

Surface waters are a receptacle for runoff and urban effluents that release existing and emerging contaminants
Residue was redissolved in 150 μl methanol:water (20:80) containing 20 mM ammonium acetate
The group exposed to 4 μg L−1 of MTX had taken up concentrations of 0.219 ± 0.268 ng g−1 of MTX, while higher values of 1.11 ± 0.24 ng g−1 and 2.53 ± 0.59 ng g−1 were calculated for exposure to 20 and 100 μg L−1, respectively (Table 4)

Summary

Introduction

Surface waters are a receptacle for runoff and urban effluents that release existing and emerging contaminants. 2011; Mahnik et al 2004) These pharmaceuticals are not an exception in terms of fate in treatment plants, i.e., they are weakly retained or degraded at WWTPs and largely released in effluent receiving waters (Azuma et al 2015; Česen et al 2015; Haddad et al 2015; Kosjek et al 2013; Lenz et al 2007; Mukherjee et al 2020; Zhang et al 2013). There have been only a few studies in which several wastewater treatments have been tested for cytostatics (Česen et al 2015; Chen et al 2019; FerrandoCliment et al 2014; Lutterbeck et al 2015; Ofiarska et al 2016; Russo et al 2018) The results of these experiments demonstrate high variability in treatment efficacy for cytostatics, and treatment combinations are more effective than a single treatment. These studies demonstrated the complexity of treating cytostatic as no treatment plants are designed to treat all pharmaceuticals

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