Iron deficiency anemia is the most common nutritional deficiency worldwide, affecting nearly 1 billion people. There are currently 6 brand (Ferinject, Feraheme, Venofer, Ferrlecit, Dexferrum, InFed) and 1 generic (Sodium Ferric Gluconate (SFG) referencing Ferrlecit) FDA approved intravenous iron products on the market for the treatment of iron deficiency anemia. These products are colloidal nanoparticles composed of a polynuclear iron(III)-(oxy)hydroxide core, stabilized by carbohydrate ligands. There is concern that the generic iron formulations may have a different safety profile from their reference listed drug (RLD) products due to differences in physicochemical properties, which in turn could cause them to release iron differently leading to toxicity.<br/><br/>Under normal conditions, the iron released by the IV iron drug is bound to the protein transferrin and then transported into the cell via the transferrin receptor pathway. Under iron overload conditions, however, transferrin becomes saturated, and the remaining iron called “labile iron” is taken up by the cell via non-iron specific pathways. Labile iron, once it enters the cell, can promote the production of reactive oxygen species which can damage proteins, DNA, and lipids. Thus, it is critical that the IV iron products do not produce excessive labile iron in circulation.<br/><br/>A key gap in our understanding is how iron is released from iron nanoparticle drugs. Current methods do not allow for the iron speciation of the nanoparticle drug nor the quantification of labile iron to be measured. We have developed novel approaches using inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography (LC) coupled ICP-MS. LC-ICP-MS allow for the simultaneous identification and quantification of all iron species in blood plasma in their native form. This assay will be presented along with pilot data on plasma from patients treated with SFG.

Elusive labile iron: Bioanalytical techniques to measure iron speciation in human plasma

255th National Meeting (2018)

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