Abstract:
Three sensitive, selective, and precise stability indicating methods for the determination of the X-ray contrast agent, diatrizoate sodium (DTA), in the presence of its acidic degradation product (highly cytotoxic
3,5 diamino metabolite) and in pharmaceutical formulation were developed and validated. The first
method is a first derivative (D1) spectrophotometric one, which allows the determination of DTA in
the presence of its degradate at 231.2 nm (corresponding to zero crossing of the degradate) over a concentration range of 2–24 lg/mL with mean percentage recovery 99.95 ± 0.97%. The second method is the
first derivative of the ratio spectra (DD1) by measuring the peak amplitude at 227 nm over the same concentration range as D1 spectrophotometric method, with mean percentage recovery 99.99 ± 1.15%. The
third method is a TLC-densitometric one, where DTA was separated from its degradate on silica gel plates
using chloroform:methanol:ammonium hydroxide (20:10:2 by volume) as a developing system. This
method depends on quantitative densitometric evaluation of thin layer chromatogram of DTA at
238 nm over a concentration range of 4–20 lg/spot, with mean percentage recovery 99.88 ± 0.89%. The
selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DTA in pharmaceutical dosage forms without interference from other dosage form additives. The results were statistically compared with the official US
pharmacopeial method. No significant difference for either accuracy or precision was observed.
