Rapid and sensitive speciation analysis of established and emerging gadolinium-based contrast agents in the aquatic environment by IC-ICP-MS

Abstract

Gadolinium-based contrast agents (GBCAs) are well established and frequently used to enhance image contrast in magnetic resonance imaging (MRI). After their administration, GBCAs leave the patient's body unmetabolised, enter the wastewater system with insufficient elimination during wastewater treatment, and get discharged into the aquatic environment as trace-level contaminants. An increasing number of applications and rising environmental concentrations with unknown ecotoxicological long-term effects express the need for sensitive and selective GBCA speciation analysis. Furthermore, the recent approval of the newly developed GBCA gadopiclenol with a reduced Gd dose and generally updated regulations might alter environmental discharge and require advanced chromatographic separation. A rapid and automated GBCA speciation analysis method based on ion chromatographic (IC) separation and elemental detection with inductively coupled plasma-mass spectrometry (ICP-MS) of six clinically relevant GBCAs, including gadopiclenol, was achieved in 175 s. Excellent single-digit pico-molar (pM) detection limits and high matrix robustness for macrocyclic GBCAs allow the straightforward analysis of surface waters. River water samples from the densely populated Ruhr metropolitan area in Germany showed substantial GBCA contamination with up to 300 nM total GBCA concentrations in the river Lippe, exceeding typical concentrations in the aquatic environment. The combination of total metal analysis and GBCA speciation analysis allowed tracing different contaminants to potential discharge sources and investigating their environmental fate. Additionally, an unidentified species of undetermined origin was detected. Although the new GBCA gadopiclenol was not detected in the aquatic environment, the method is capable of ongoing monitoring and further studies on its stability and environmental behaviour.