Prussian blue, ferric hexacyanoferrate is approved for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide makes up 35-40% of Prussian blue's molecular composition; thus, cyanide may be released during transit through the digestive tract under physiological pH conditions. The purpose of this study is to assess the long-term stability of Prussian blue drug products and active pharmaceutical ingredients and its impact on cyanide release. The study involves the determination and comparison of the loss in water content and cyanide released from Prussian blue under pH conditions that bracket human physiological exposure. Test samples of active pharmaceutical ingredient and drug product were stored for 10 years at ambient temperatures that mimic warehouse storage conditions. Water loss from Prussian blue was measured using thermogravimetric analysis. An in vitro physiological pH model that brackets gastric exposure and gastrointestinal transit was utilized for cyanide release. Prussian blue was incubated in situ at pH: 1.0, 5.0, and 7.0 @ 37°C for 1-24 h. Cyanide was measured using a validated colorimetric method by UV-Vis spectroscopy. Although the water content (quality attribute) of Prussian blue active pharmaceutical ingredient and drug product decreased by about 10.5% and 13.8%, respectively, since 2003, the cyanide release remained comparable. At pH of 7.0 for 24 h cyanide released from active pharmaceutical ingredient-1 was 21.33 ± 1.76 μg/g in 2004, and 28.45 ± 3.15 μg/g in 2013; cyanide released from drug product-1 was 21.89 ± 0.56 μg/g in 2004, and 27.31 ± 5.78 μg/g in 2013. At gastric pH of 1.0 and upper gastrointestinal pH of 5.0, the data for active pharmaceutical ingredients and drug products were also comparable in 2013. The cyanide release is still pH-dependent and follows the same trend as observed in 2003 with minimum release at pH of 5.0 and maximal release at pH of 1.0. In summary, this is the long-term stability study of Prussian blue which correlates cyanide release to water loss. Cyanide released from Prussian blue was maximum at pH of 1.0 (47.47 μg/g) and minimum at pH of 5.0-7.0 (20.01 μg/g). Based on maximal dose, maximal residence time in stomach and intestine, the maximal cyanide released from Prussian blue is about 1.31 mg, which is far below the minimal lethal dose of cyanide of 50 mg, and therefore does not present a safety concern following long-term storage.