Quantitative evaluation of the thallium binding of soluble and insoluble Prussian blue hexacyanoferrate analogs: A scientific comparison based on their critical quality attributes.
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abstract
There has been a long-standing discussion in the scientific literature on the thallium (Tl) binding capacity of ferric hexacyanoferrate (insoluble) and potassium hexacyanoferrate (soluble) forms of Prussian blue (PB). The literature sometime suggests that the soluble form of PB should be used to treat thallium poisoning, instead of the FDA approved insoluble form of PB. The literature debate is further complicated by the lack of fundamental characterization data such as critical quality attributes (CQAs) that clearly define the analog forms. The purpose of this study is to compare, the binding capacity of soluble and insoluble PB analogs with the same CQAs (particle size/distribution and water content). Water content and particle size/particle distribution were determined by TGA, and solid-state laser diffraction particle sizing. Thallium binding studies were conducted at physiological pH to determine the maximal binding capacity (MBC) at equilibrium. Multiple linear regression and principal component analysis was also used for multivariate data analysis. Results indicate that insoluble and soluble analogs, with similar quality attributes, have nearly identical, MBC binding capacities of (441.5mg/g) for insoluble vs soluble (458.4mg/g). However, when both analog forms with different CQAs such as water, particle size were compared, results indicated significantly higher or lower thallium binding levels. In conclusion, it is essential that the FDA approved iron form with well-defined CQAs is used to treat thallium poisoning and radioactive thallium metal contamination for consistent therapeutic outcomes.
