Quantification of Free and Chelated Gadolinium Species in Nanoemulsion-Based Magnetic Resonance Imaging Contrast Agent Formulations using Hyphenated Chromatography Methods: Version 1.0

Gadolinium-based magnetic resonance imaging (MRI) contrast agent (CA) formulations have been routinely applied in the clinical setting to improve differentiation among neighboring tissues of interest. Although the free gadolinium ion has potentially toxic effects , complexation of the ion by various ligands has been shown to improve acute tolerance. Nanoemulsion-based CAs, which use liposomal ligands to chelate the gadolinium, have shown promise as highly potent contrast agents, due to their accommodation of a significantly higher gadolinium payload, improved relaxivities, and reduced incidents of release of gadolinium ions compared to traditional CAs. With the advent of these new types of gadolinium-ligand complexes, it remains crucial to measure the amounts of total, bound, and uncomplexed gadolinium in CA formulations. This technical procedure defines the analytical protocols for gadolinium speciation measurements in liposomal MRI CA formulations that contain emulsifiers, surfactants, and therapeutic agents.