• Home
  • Search Results
  • Long-term stability study of Prussian blue-A quality assessment of water content and cyanide release.

Long-term stability study of Prussian blue-A quality assessment of water content and cyanide release.

Clinical toxicology (Philadelphia, Pa.) (2015-01-23)
A Mohammad, Y Yang, M A Khan, P J Faustino
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrochloric acid, ACS reagent, 37%
Sigma-Aldrich
Hydrochloric acid, ACS reagent, 37%
Sigma-Aldrich
Sodium hydroxide, reagent grade, ≥98%, pellets (anhydrous)
Sigma-Aldrich
Potassium hydroxide, ACS reagent, ≥85%, pellets
Sigma-Aldrich
Sodium hydroxide solution, 50% in H2O
Sigma-Aldrich
Sodium hydroxide, ACS reagent, ≥97.0%, pellets
Sigma-Aldrich
Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H2O
Sigma-Aldrich
Sodium hydroxide, BioXtra, ≥98% (acidimetric), pellets (anhydrous)
Sigma-Aldrich
Hydrogen chloride solution, 4.0 M in dioxane
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
Sigma-Aldrich
Hydrochloric acid, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., fuming, ≥37%, APHA: ≤10
Sigma-Aldrich
Potassium hydroxide, reagent grade, 90%, flakes
Sigma-Aldrich
Potassium hydroxide solution, 45 wt. % in H2O
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
Supelco
Sodium hydroxide concentrate, 0.1 M NaOH in water (0.1N), Eluent concentrate for IC
Sigma-Aldrich
Sodium hydroxide, puriss., meets analytical specification of Ph. Eur., BP, NF, E524, 98-100.5%, pellets
Sigma-Aldrich
Potassium hydroxide, semiconductor grade, pellets, 99.99% trace metals basis (Purity excludes sodium content.)
Sigma-Aldrich
Hydrogen chloride solution, 2.0 M in diethyl ether
Supelco
Sodium hydroxide solution, 49-51% in water, eluent for IC
Supelco
Potassium hydroxide solution, volumetric, 8.0 M KOH (8.0N)
Sigma-Aldrich
Potassium hydroxide, BioXtra, ≥85% KOH basis
Supelco
Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
Sigma-Aldrich
Sodium hydroxide, reagent grade, 97%, powder
Sigma-Aldrich
Potassium hydroxide, ≥85% KOH basis, pellets, white
Sigma-Aldrich
Sodium hydroxide solution, 5.0 M
Sigma-Aldrich
Hydrochloric acid, meets analytical specification of Ph. Eur., BP, NF, fuming, 36.5-38%
Supelco
Potassium hydroxide concentrate, 0.1 M KOH in water (0.1N), Eluent concentrate for IC
Sigma-Aldrich
Sodium hydroxide, puriss. p.a., ACS reagent, reag. Ph. Eur., K ≤0.02%, ≥98%, pellets