Measuring Uncertainty Using Different Approaches: A Case Study for Acetaminophen Quantification

Abstract

Abstract Investigation of out-of-specification analytical results is laborious, time-consuming, and costly and must be well documented. However, an analytical result is not complete unless reported with its measurement uncertainty. Here, we compare four different approaches for measurement uncertainty estimation used in acetaminophen quantification in pharmaceutical drug products. Measurement uncertainties were estimated using a repeatability and reproducibility study, Eurachem/Citac guidelines, Monte Carlo simulations, and a spreadsheet method. These different approaches provided similar results. However, they differed by the sources of uncertainties considered, by the procedures of calculation, and by the effort required in routine applications. Nevertheless, all four approaches were successful in assessing conformity of acetaminophen content in pharmaceutical drug products and may be used in assessing pharmaceutical equivalence.