The effect of glucose and copper on the stability of diatrizoic acid.

Hypaque Sodium Oral Solution is used as a X-ray contrast agent. The active ingredient is diatrizoate sodium. Several bottles of drug product were found to contain elevated levels of inorganic iodide, ranging from 0.001% (w/v) to 0.036% (w/v). The USP specification is no more than 0.02% w/v. The formulation contains sucrose as a sweetener and as a viscosity modifier. It was found that elevated levels of iodide were directly related to the amount of glucose found in the formulation. Glucose is a reducing sugar which can be generated by the decomposition of sucrose. Solution stress studies containing diatrizoate sodium and varying amounts of glucose and copper were conducted at three different pH values: 6, 7 and 8 in phosphate buffer at 60 degrees C. The decomposition of diatrizoate sodium was monitored by HPLC. The greatest amount of decomposition occurred in those solutions prepared in pH 8 phosphate buffer and containing both copper and glucose. It is suggested that glucose reacts with copper to form an activated species, which reacts to displace an iodide.