Abstract
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.
Highlights
Iron is an essential component of every cell in the body
non-transferrin bound iron (NTBI) values were consistently much higher at all time points and especially the critical early time points. These results indicate that bleomycin pulls iron either from transferrin bound or drug bound iron or both
A simple and reproducible ultra-filtration technique with sensitive detection was developed for the simultaneous quantification of NTBI, transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) within a very small sample volume
Summary
Iron is an essential component of every cell in the body. Its most critical role is as a component of hemoglobin in the transport and storage of oxygen [1]. Iron supplements are widely administered to treat iron deficiency anemia, in chronic diseases such as kidney disease [1], heart failure [3] or inflammatory bowel disease [4]. In these disease conditions, intravenous (IV) iron colloidal products are being used to treat serious iron deficiency anemias those requiring dialysis
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