Development of an iron quantification method using nuclear magnetic resonance relaxometry

Abstract

Biocompatibility has prompted a great amount of research in iron oxide nanoparticles (IONPs) as alternative magnetic resonance imaging (MRI) contrast agents. Iron concentration analysis is a key parameter to determine the relaxivities of IONPs as MRI contrast agents. Currently available methods for iron quantification are mainly inductively coupled plasma mass spectrometry (ICP-MS) and ferrozine-based iron assays. ICP spectrometry may not be easily accessible for routine analysis while iron assays are highly sensitive to sample preparation. In this paper, we present an alternative method for quantifying iron concentration using nuclear magnetic resonance (NMR) relaxometry, a technique commonly used for developing MRI contrast agents. To quantify iron concentration with NMR, a standard curve of relaxation rate versus iron concentrations was created to obtain the relaxivity of Fe3+ iron in solution. After dissolving IONPs in an acid, the iron concentration of the solution can be obtained using the relaxation times and the relaxivity of Fe3+ iron from the standard curve. The accuracy and sensitivity of this NMR method were verified by comparing with ICP analysis and ferrozine-based iron assays. Results indicate that this NMR method for iron concentration analysis was accurate for concentrations as low as 0.005 mM. In addition, the relaxivity of Fe3+ iron was sensitive to the type of acids to dissolve the IONPs, indicating that the same acid should be used for sample dissolution and the standard curve.