Interference of gadolinium-based contrast agents on colorimetric calcium assays

The aim of this study was to evaluate the potential interference of five gadolinium-based contrast agents (GBCAs), gadodiamide (Omniscan®), gadobenate dimeglumine (Multihance®), gadoxetate disodium (Primovist®), gadobutrol (Gadovist®), and gadoteridol (Prohance®), on three clinical laboratory widely used colorimetric calcium assays including the newly developed 5-nitro-5'methyl-l,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (NM-BAPTA) method.

Plasma was collected from healthy volunteers aged 23-52, and spiked with varying concentrations of the five GBCAs. Calcium determinations were performed in duplicates using the o-cresolphthalein complexone (OCP), arsenazo-III dye, and NM-BAPTA methods on the Roche Integra 400, Abbott Architect 16000, and Roche Modular P automated analyzers respectively.

Gadobenate dimeglumine, gadobutrol, and gadoteridol did not interfere with any of the assays. There was a small positive bias (8%, p<0.01) at a very high concentration (25mmol/L) of gadoxetate disodium when calcium was assayed using the arsenazo-III method. Gadodiamide at a very high concentration (50mmol/L) induced a significant positive bias (16%, p<0.01) on calcium when measured using the NM-BAPTA method; however a much larger bias (90%, p≪0.01) was observed when calcium was measured using the arsenazo-III method. Significant interferences in calcium measurements using the OCP method began at gadodiamide concentrations as low as 0.5mmol/L (-9%, p<0.01). This negative bias was more pronounced at higher gadodiamide concentrations.

Of all 5 GBCAs tested, only gadodiamide showed significant interference on the OCP calcium assay at clinically relevant concentrations. The NM-BAPTA assay showed minimum interference with the five GBCAs and demonstrated equal or better performance than the OCP and the arsenazo-III methods in terms of interference with GBCAs.