Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Chromatographic Methods for the Quantification of Free and Chelated Gadolinium Species in MRI Contrast Agent Formulations



Danielle Cleveland, Stephen E. Long, Lane C. Sander, William C. Davis, Karen E. Murphy, Catherine A. Rimmer, Lorena Francini, Anil K. Patri


Speciation measurements of gadolinium in liposomal MRI contrast agents are complicated by the presence of emulsifiers, surfactants, and therapeutic agents in the formulations. The present paper describes two robust, hyphenated chromatography methods for the separation and quantification of gadolinium in nanoemulsion-based contrast agent formulations. Three potential species of gadolinium, free gadolinium ion, gadolinium chelated by diethylenetriamine pentaacetic acid (Gd-DTPA), and gadolinium chelated by diethylenetriamine pentaacetic acid-phosphatidylethanolamine (Gd-DTPA-PE), were present in the contrast agent formulations. The species were separated by reversed-phase chromatography (RP-HPLC), or by high pressure size exclusion chromatography (HPSEC). For RP-HPLC, fluorescence detection and post-column, online isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) were used to measure the amount of gadolinium in each species. Online ID-ICP-MS and triple-spike species-specific isotope dilution (SID) ICP-MS were used in combination with the HPSEC column. The results indicated that some inter-species conversions and degradation had occurred within the samples, and that SID-ICP-MS should be used to provide the most reliable measurements of total and speciated gadolinium. However, fluorescence and online ID-ICP-MS might usefully be applied as qualitative, rapid screening procedures for the presence of free gadolinium ions.
Analytical Chemistry


gadolinium speciation, MRI contrast agent formulations, isotope dilution analysis, species-specific isotope dilution analysis, ICP-MS, fluorescence detection, high pressure size exclusion chromatography, reversed-phase chromatography, nanoemulsion, DTPA-PE, liposome


Cleveland, D. , Long, S. , Sander, L. , Davis, W. , Murphy, K. , Rimmer, C. , Francini, L. and Patri, A. (2010), Chromatographic Methods for the Quantification of Free and Chelated Gadolinium Species in MRI Contrast Agent Formulations, Analytical Chemistry, [online], (Accessed April 17, 2024)
Created October 3, 2010, Updated October 13, 2017