Analytical Interference in Serum Iron Determination Reveals Iron Versus Gadolinium Transmetallation With Linear Gadolinium-Based Contrast Agents

Objectives: The purposes of this study were to evaluate the risk for analytical interferencewith gadolinium-based contrast agents (GBCAs) for the colorimetric measurement of serum iron (Fe3+) and to investigate the mechanisms involved. Materials and Methods: Rat serum was spiked with several concentrations of all molecular categories of GBCAs, ligands, or ‘‘free’ ’ soluble gadolinium (Gd3+). Serum iron concentration was determined by 2 different colorimetric methods at pH 4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 an-alyzer). Secondly, the cause of interference was investigated by (a) adding free soluble Gd3+ orMn2+ to serum in the presence of gadobenic acid or gadodiamide and (b) electrospray ionization mass spectrometry. Results: Spurious decrease in serum Fe3+ concentration was observed with all linear GBCAs (only with the Vitros DT60 technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free soluble Gd3+. Spurious hyposideremia was also observed with the free ligands present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and gadodiamide (ie, diethylene triamin