Drug stability testing by monitoring drug and degradate levels by liquid chromatography.
A cephalosporin antibiotic and its primary degradation product can be separated by a mixed retention mechanism using an ion exchange column and a mobile phase containing acetonitrile and aqueous sodium phosphate. Assay ruggedness, specificity, linearity of response, and standard-sample stability are evaluated and found to be adequate for the desired application. Drug degradation at room temperature in formulations containing citrate and dextrose is found to be roughly first order; fit of the first order rate expression model is better when gain in degradate levels is used as opposed to the direct measurement of drug loss, especially when the magnitude of drug loss is small. The greater accuracy of projections based on the measurement of degradate gain is related to the effect of the imprecision of the analytical measurement on the accuracy of the model.