Speciation of gadolinium in gadolinium-based magnetic resonance imaging agents by high performance liquid chromatography inductively coupled plasma optical emission spectrometry

Abstract

A highly sensitive and robust method for the determination of six gadolinium species by reversed-phase liquid chromatography coupled with inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES) has been developed. The gadolinium(III) complexes, Gd–DTPA²⁻, Gd–DOTA¹⁻, Gd–HP–DO3A, Gd–DTPA–BMA and Gd–DTPA–BMEA were analyzed by reversed-phased chromatography with a mobile phase of 10 mM ammonium acetate at pH 7.0. The Gd–BOPTA²⁻ gadolinium(III) complex was separated on a C₁₈ reversed-phase column with a mobile phase of 10 mM ammonium acetate and 5% acetonitrile at pH 7.0. The total time for the analysis took less than 15 minutes for each gadolinium(III) complex with isocratic elution at a flow rate of 1.0 mL min⁻¹. The calibration curves for the gadolinium(III) complexes were linear over the concentration range of 0.393 to 78.625 µg mL⁻¹ (2.5 to 500 µM). The solution detection limits of the six gadolinium(III) complexes obtained by HPLC-ICP-OES were between 8 and 35 ng Gd mL⁻¹ (0.05 to 0.2 µM) using an injection volume of 50 µL. The developed HPLC-ICP-OES method was successfully applied for the determination of gadolinium species in magnetic resonance contrast media solutions and spiked human serum solutions. The precision for 3 replicate determinations at the 3.93 µg mL⁻¹ (25 µM) Gd level was less than 5% RSD for the six gadolinium(III) complexes in water and human serum. The recoveries were between 95 and 103% for the gadolinium(III) complexes in human serum solutions. Chromatographic profiles were obtained for Magnevist™, Dotarem™, ProHance™, Omniscan™, Optimark™ and MultiHance™ contrast media solutions.