Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection
Murali K. Matta,
Christopher R. Beekman,
Adarsh Gandhi,
Suresh Narayanasamy,
Christopher D. Thomas,
Adil Mohammad,
Sharron Stewart,
Lin Xu,
Ashok Chockalingam,
Katherine Shea,
Vikram Patel,
Rodney Rouse
Affiliations
Murali K. Matta
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Christopher R. Beekman
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Adarsh Gandhi
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Suresh Narayanasamy
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Christopher D. Thomas
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Adil Mohammad
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, Division of Product Quality Research, Silver Spring, MD 20993, USA
Sharron Stewart
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Lin Xu
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Ashok Chockalingam
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Katherine Shea
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Vikram Patel
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
Rodney Rouse
U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science, Silver Spring, MD 20993, USA
A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI), transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) in the same rat serum sample after intravenous (IV) administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®). Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2) of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK) study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.
