Assay and purity analysis of diatrizoate sodium in drug product by LC

An LC procedure was developed to separate diatrizoate sodium from three known impurities. These impurities are 2,4- and 2,6-diiodo-3,5-diacetamidobenzoic acid (DDZA), and the free amine (5-acetamido-3-amino-2,4,6-triiodobenzoic acid). The separation was achieved using a Hamilton, PRP-X100, anion exchange column. The retention of diatrizoate sodium and the impurities was dependent on pH, potassium chloride concentration and phosphate concentration. Increasing any of these mobile phase modifiers decreased the retention time of all of the components. The eluent for assay and purity determination of drug product consisted of 0.1 M potassium chloride and 0.05 M potassium phosphate dibasic in water/acetonitrile (900:100). The mean concentration of diatrizoate sodium in Hypaque Sodium 50% determined over 3 days was 102.3% of label claim with an R.S.D. of 1.3. The accuracy of the purity method, determined by spiking known amounts of the impurities at five concentrations ranging from 0.025 to 0.06% (w/w) into drug product, was 100.1% for DDZA and 94.2% for the free amine. The decomposition of diatrizoate sodium in 0.1 N potassium hydroxide at 85 degrees C followed pseudo first-order kinetics. The calculated half-life was 2 days.