Patients with Chronic Kidney Disease experience severe anemia that must be treated with intravenous therapy-iron preparations. There are currently 6 brand and 1 generic FDA approved iron products on the market; all of which are colloidal nanoparticles composed of a polynuclear iron(III)-(oxy)hydroxide core stabilized by a carbohydrate ligand. Delivery of intravenous therapy-iron preparations affects iron homeostasis in the cell. Under normal conditions, the iron is chelated by transferrin in the blood plasma. Transferrin then traffics the iron into the cell, via the transferrin receptor pathway, thereby providing iron as a protein co-factor. Under iron overload conditions, the transferrin receptor becomes saturated, and the remaining iron, which is collectively called ‘non-transferrin bound iron’ or NTBI, is taken up by the cell via non-iron specific pathways (e.g. DMT, ZIP). Once NTBI has enters the cell, it promotes production of reactive oxygen species (ROS) via the Haber-Weiss reaction damaging proteins, DNA and lipids. Thus it is critical that the intravenous therapy-iron products used to treat anemia deliver the optimal level of iron. We are developing high-through-put bioanalytical assays to measure total iron (TI), transferrin bound iron (TBI), and NTBI in plasma samples. This includes a high-throughput method to measure total iron (TI) concentrations in blood plasma the utilizes inductively coupled plasma mass spectrometry (ICP-MS), a liquid chromatography (LC) coupled ICP-MS protocol to measure TBI concentration, and a chelation-ICP-MS strategy to measure NTBI. Our efforts in this area along with some work aimed at measuring labile iron (LI) will be presented. These assays will be applied to a clinical trial in which the brand and generic sodium ferric gluconate drug products will be compared.

Bioanalytical approaches to measure iron speciation in plasma of patients treated with iron-nanoparticle drug products

251st National Meeting (2016)

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