title: A long-term stability study of Prussian blue: A quality assessment of water content and cesium binding.
abstract: Prussian blue (PB) is the active pharmaceutical ingredient (API) of Radiogardase, the first approved medical countermeasure for the treatment of radiocesium poisoning in the event of a major radiological incident such as a "dirty bomb" or nuclear attack. The purpose of this study is to assess the long-term stability of Prussian blue drug products (DPs) and APIs under laboratory storage condition by monitoring the loss in water content and the in vitro cesium binding. The water content was measured by thermal gravimetric analysis (TGA). The in-vitro cesium binding study was conducted using a surrogate model to mimic gastric residence and intestinal transport. Free cesium was analyzed using a validated flame atomic emission spectroscopy (AES) method. The binding equilibrium was reached at 24h. The Langmuir isotherm was plotted to calculate the maximum binding capacity (MBC). Comparison of the same PB samples with 2003 data samples, the water content of both APIs and DPs decreased on an average by approximately 12-24%. Consequently, the MBC of cesium was decreased from 358mg/g in 2003 to 265mg/g @ pH 7.5, a decrease of approximately 26%. The binding of cesium is also pH dependent with lowest binding at pH 1.0 and maximum binding at pH 7.5. At pH 7.5, the amount of cesium bound decreased by an average value of 7.9% for APIs and 8.9% for DPs (for 600ppm initial cesium concentration). These findings of water loss, pH dependence and decrease in cesium binding are consistent with our previously published data in 2003. Over last 10 years the stored DPs and APIs of PB have lost about 20% of water which has a negative impact on the PB cesium binding, however PB still meets the FDA specification of >150mg/g at equilibrium. The study is the first quantitative assessment of the long-term stability of PB and directs that proper long-term and short-term storage of PB is required to ensure that it is safe and efficacious at the time of an emergency situation.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States.
authors.forename: Adil
authors.initials: A
authors.lastname: Mohammad
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993, United States. Electronic address: patrick.faustinop@fda.hhs.gov.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Faustino
mesh_terms: D002138:Calibration; D002586:Cesium / Q000737:chemistry*; D005295:Ferrocyanides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D012015:Reference Standards; D013054:Spectrophotometry, Atomic; D014867:Water / Q000032:analysis*
chemical_list: D005295:Ferrocyanides; D014867:Water; D002586:Cesium; C000170:ferric ferrocyanide
keywords: Cesium binding; Moisture content; Product Quality; Prussian blue; Stability; Strategic National Stockpiles