On-line HPLC-electrospray ionization mass spectrometry: a pharmacological tool for identifying and studying the stability of Gd3+ complexes used as magnetic resonance imaging contrast agents.

The identification of MRI contrast agents (CAg) as gadolinium complexes often used at very low concentrations in Pharmacology was carried out by ESI-MS or HPLC-ESI-MS. Firstly, Omniscan, Dotarem and Magnevist were tested. In these compounds, the Gd3+ ion must be solidly chelated by linear or macrocyclic ligands because of the severe toxicity of the free Gd3+. Spectra were obtained at low voltage, preserving the non-covalent binding integrity of the complexes, and at various higher voltages showing the progressive destruction of the complexes. Secondly, a direct reaction of these drugs with the oxidative human neutrophil production, induced in vitro by Phorbol 12-myristate 13-acetate enhancing the respiratory burst, was investigated. This was done to mimic what happens in the case of inflammatory diseases, or infection, or when people are likely to develop anaphylactoid reactions, as the i.v. injection of CAg causes contact between the complexes and neutrophils in the blood. Analysis by HPLC-ESI-MS coupling did not show any direct reaction between Gd complexes and the chemical compounds in the neutrophil oxidative metabolism, even if uncertainty remains as regards meglumine salt. HPLC-ESI-MS is a good way of visualizing characteristic, Gd isotopic distribution and of following its associations in biological samples.