Development and Validation of an Ion-Exclusion Chromatographic Method for the Quantitation of Organic Acids in Complex Pharmaceutical Products

Abstract

Effective quantitation of organic acids (acetic, malic, and lactic acids) present in total parenteral nutrition (TPN) pharmaceutical products for final product release purposes requires accuracy, precision, and specificity but less than optimal sensitivity. A chromatographic method relying on ion-exclusion separation and low-wavelength ultraviolet detection has been developed and validated to quantitate these organic acids in matrices containing 10-fold or greater excesses of other constituents (sugars, amino acids, and other inorganic salts) with no sample preparation other than dilution. Mobile phases at slightly different pH values effectively eliminates matrix-related interferences that were observed during the analysis of several products. The validation procedure used is discussed in terms of its strategy and results. Ultimately, the assay is found to be appropriate for the release testing of several compositionally diverse TPN products.