Analysis of Gadolinium-Based MRI Contrast Agents Using IC-ICP/MS Technique

Gadolinium contrast agents, which are mainly administered via intravenous injection, exhibit excellent in vitro and in vivo stability. These agents have a half-life of about two hours. They are excreted from the body unchanged via the kidney-urine pathway and passed into wastewater.

Molecular structure of Gadobutrol (Gadovist) - gadolinium containing MRI contrast agent. Image Credits: Raimundo79/Shutterstock.com

Flocculation with Al³⁺ or Fe³⁺ salts is carried out in municipal sewage treatment plants to improve the settling behavior of suspended and dissolved colloidal materials. These trivalent metal ions that are added compete with Gd³⁺ ions for the organic ligands.

IC-ICP/MS analysis of gadolinium-based MRI contrast agents

Depending on the thermodynamic complex stability, addition of the trivalent metal salts may cause transmetallation or recomplexing in the MRI contrast agents, resulting in the release of toxic Gd³⁺ ions. Metal exchange in gadolinium chelates occurs as part of iron flocculation (Künnemeyer, J., 2009; Kümmerer, 2008).

This article examines the degree to which toxic gadolinium ions are released from MRI chelates as a result of flocculation carried out in wastewater treatment. IC-ICP/MS is used to carry out gadolinium speciation.

Results

Well-separated peaks for Magnevist and Gadovist are generated by IC-ICP/MS analysis on the anion-exchange column. Being an uncharged, polar compound, Gadovist elutes after just a few minutes, whereas the twice negatively charged Magnevist is retained more strongly and elutes much later, as shown in Figure 1.

Figure 1. Chromatograms of polar and electrically neutral Gadovist and of ionic Magnevist (both 100 μg/L). Column: Metrosep A Supp 3 - 250/4.6; eluent: 7.2 mmol/L Na₂CO₃, 6.8 mmol/L NaHCO₃; flow rate: 1.0 mL/min; m/z 156, 158, 160

The extent of transmetallation is reflected by the concentrations of the competing Gd(III) and Fe(III) ions on the polyaminopolycarboxylate ligands. This showed that displacement of gadolinium increased as the concentration of Fe³⁺ ions increased. This effect was stronger for Magnevist than for Gadovist. According to the higher thermodynamic stability constant of the iron(III)-DTPA complex (log K = 28.6), Magnevist (log K = 23.0) can be recomplexed to about 80% by Fe³⁺ concentrations of just 5 mg/L (Künnemeyer, J., 2009).

Over 90% of the chelate complexes are in the form of iron chelate complexes, with an Fe³⁺ concentration of 20 mg/L, whereas, Gadovist releases less than 10% of the Gd³⁺ ions, even at higher concentrations of Fe³⁺ ions. The complex center of Gadovist is effectively shielded against the competing Fe³⁺ ions by the crownether-like polyaminopolycarboxylic acid ligand, which is spherically arranged around the gadolinium. This largely prevents transmetallation. On the other hand, the linear DTPA ligands of Magnevist only weakly protect the central atom, so gadolinium is largely substituted by iron, resulting in the formation of the more stable iron (III) complex (Bianchi, A., 2000).

Gadolinium – further applications with IC-ICP/MS

Speciation and Isotope Dilution Analysis of Gadolinium-Based Contrast Agents in Wastewater - Telgmann, L.; Wehe, C.A.; Birka, M.; Künnemeyer, J.; Nowak, S.; Sperling, M.; Karst, U. (2012) Environ. Sci. Technol. 46(21), 11929–11936.

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