A long-term stability study of Prussian blue: A quality assessment of water content and cesium binding

•The long-term stability of Prussian blue was investigated.•Well characterized pharmaceutical samples were stored for 10 years.•Prussian blue undergoes physiochemical changes characterized by the loss of water.•A decrease in cesium binding indicated product quality was negatively affected.•The study is the basis for a quantitative risk assessment of stockpiled products.

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 24 h. 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 358 mg/g in 2003 to 265 mg/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 600 ppm 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 >150 mg/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.

Graphical abstractCesium binding for several Prussian blue APIs exposed to 600 ppm initial cesium concentration for 24 h at maximal binding at pH 7.5. A comparison of 2003–2013 data. API-2 represents sub-potimal water content.Figure optionsDownload full-size imageDownload as PowerPoint slide