Development and validation of an assay for citric acid/citrate and phosphate in pharmaceutical dosage forms using ion...

The paper describes the development and validation of a simple, rapid, accurate, and sensitive ion chromatographic procedure to assay total citrate (citric acid/citrate) and phosphate in nine dosage forms. The dosage forms chosen represent all dosage forms in USP27-NF22 for which the respective monographs require an assay for either citric acid/citrate or citric acid/citrate and phosphate. Citrate and phosphate were separated in <10min by a hydroxide-selective column using anion-exchange chromatography with a 20mM potassium hydroxide eluent and detected by suppressed conductivity. The method showed linear responses over the concentration ranges 0.2-100microg ml(-1) (r(2) > 0.9990) for citrate and 0.2-60microg ml(-1) (r(2) = 0.9999) for phosphate, with limits of quantitation (signal-to-noise (S/N) = 10) of 0.2microg ml(-1) for both analytes. The accuracy of the procedure, determined by spiked recovery measurements, was within 95-105%. The intraday and the interday precision were demonstrated by the relative standard deviations (R.S.D.) of <1 and <2%, respectively, for both analytes. The ruggedness was determined by a full factorial design using analyst, equipment, column lot, and eluent preparation procedure as variables. The results show an overall R.S.D. of <3% and that an electrolytically generated 20mM KOH eluent produces assay results equivalent to a manually prepared 20mM NaOH eluent.