Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. D. High pressure liquid chromatographic methods.

Precision parameters of high pressure liquid chromatographic methods approved by AOAC for the analysis of drug dosage forms were recalculated on a consistent statistical basis, using the computer program "FDACHEMIST." Eleven collaborative studies of 12 compounds in 66 dosage forms analyzed by an average of 9 laboratories per study, with a total of 1150 determinations, were reviewed. For the approved methods and methods awaiting approval (9 studies, 11 compounds, 54 dosage forms, and 959 determinations), the average repeatability relative standard deviation (within-laboratory; RSDo) was 1.0%; reproducibility relative standard deviation (among-laboratories, including within-; RSDx) was 2.5%; the ratio RSDo/RSDx was an unusually low 0.40, with an average outlier rate of 0.6% of the reported values. The line of best fit for RSDx plotted against - log concentration increases with decreasing concentration, extending approximately from RSDx = 2% at 100% concentration to RSDx = 3.6% at 0.01% concentration, a change in RSDx of about 0.4% for each 10-fold decrease in concentration, independent of analyte and matrix.