Performance of Redox Active and Chelatable Iron Assays to Determine Labile Iron Release From Intravenous Iron Formulations.
Emerging data from global markets outside the United States, where many generic iron sucrose formulations are available, have revealed that non-US generic intravenous (i.v.) iron formulations may have iron release profiles that differ from the reference listed drug (RLD). The first generic i.v. iron approved in the United States was sodium ferric gluconate complex in 2011. We evaluated chelatable and redox labile iron assay methods to measure the amount of labile iron released from i.v. iron formulations in biorelevant matrices in vitro. The majority of published labile iron assays evaluated were not suitable for use in vitro due to overwhelming interference by the presence of the i.v. iron products. However, an optimized high-performance liquid chromatography (HPLC)-based method performed well for use in vitro labile iron detection in a biorelevant matrix. Application of this method may enhance bioequivalence evaluation of generic i.v. iron formulations in the future.
University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
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AB
Pai
General Electric Global Research Center, Niskayuna, New York, USA.
D E
DE
Meyer
General Electric Global Research Center, Niskayuna, New York, USA.
B C
BC
Bales
General Electric Global Research Center, Niskayuna, New York, USA.
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VE
Cotero
University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
M P
MP
Pai
Food and Drug Administration, Office of Generic Drugs, Silver Spring, Maryland, USA.
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N
Zheng
Food and Drug Administration, Office of Generic Drugs, Silver Spring, Maryland, USA.
W
W
Jiang
D061605:Administration, Intravenous; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001761:Bleomycin; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats
D007502:Iron Chelating Agents; D001761:Bleomycin; D007501:Iron