Measurement uncertainty for the potency estimation by rapid microbiological methods (RMMs) with correlated data

Abstract

Recently, rapid microbiological methods (RMM) have often been used to determinate the potency of antibiotic drugs. Since all the standard and sample preparations are assayed into the same analytical conditions, it is expected that the correlations among the inhibitions zone sizes are not negligible. However, the procedures adopted in uncertainty estimations do not consider the correlation of data. The aim of this work was to study the impact of the correlation of data in the measurement uncertainty and, consequently, in the risk of false conformity decisions. RMM for the determination of the potency of cephalosporin antibiotics in pharmaceutical products were performed using an agar diffusion method. The shared analytical effects on inhibition resulted in correlation of data, which significantly decreased the combined measurement uncertainties, and therefore, the risk of false conformity decisions. Due to the lognormal distribution of potency values, measurement uncertainties were reported as a multiplicative uncertainty factor (U_F). A MS-Excel spreadsheet is provided as supplementary material and may be used to estimate the measurement uncertainty and the risk of false conformity decisions for results obtained from RMM.

Keywords: Correlated uncertainty components; Measurement uncertainty; Rapid microbiological methods; Risk of false conformity decisions; Uncertainty factor.