Interference of magnetic resonance imaging contrast agents with the serum calcium measurement technique using colorimetric reagents

A possible interaction between either linear (Gd-DTPA-BMA and Gd-DTPA) or m acrocyclic (Gd-DOTA) gadolinium complexes used as magnetic resonance imagin g (MRI) contrast agents and colorimetric technique reagents for the measure ment of serum calcium was evaluated on human serum pools, and its mechanism was investigated by means of UV spectrometry and electro-spray ionization mass spectrometry (ESI-MS). The highest concentration tested was 2.5 mM (co rresponding to a putative strictly intravascular distribution of the compou nd) and the lowest dose was 0.2 mM (i.e. about two elimination half lives). Serum calcium was dosed in duplicate by conventional colorimetric techniqu es involving o-cresol-phthalein complexone (OCP) or methylthymol blue (MTB) as reagents. No interference was detected when mixing Gd-DOTA with serum, whatever the concentration. Gd-DTPA (2.5 mM) did not interfere with the col orimetric technique either. Conversely, the Gd-DTPA-BMA solution induced a concentration-related variation in apparent calcium levels. In the UV exper iments, solutions of 2.5 mM MRI contrast media were mixed with OCP or MTB a nd UV absorption spectra were recorded between 400 and 800 nm. For Gd-DOTA/ OCP and Gd-DOTA/MTB, no significant variations in the absorbance were detec ted. However, in the presence of Gd-DTPA-BMA, the absorbance of OCP and MTB showed substantial and immediate variations over time. The ESI-MS studies showed a complete displacement of Gd3+ ion in the case of Gd-DTPA-BMA. In t he presence of OCP, we observed the disappearance of Gd-DTPA-BMA and the fo rmation of the free ligand DTPA-BMA and a new complex Gd-OCP with an origin al stoichiometry of 2/2. Such a phenomenon did not occur in the case of Gd- DOTA and Gd-DTPA. The decomplexation of Gd-DTPA-BMA in the presence of OCP can probably be explained by the weaker thermodynamic stability of Gd-DTPA- BMA compared to that of Gd-DOTA and Gd-DTPA. (C) 1999 Elsevier Science B.V. All rights reserved.