How to better define the characteristics of dispersion of results in liquid chromatographic analyses through an interlaboratory study: Example of collaborative studies on ketoprofen and spiramycin

Abstract

The aim of this study was to use statistical tools, especially the analysis of variance (ANOVA), to improve knowledge of the characteristics of the dispersion of results in high-performance liquid chromatography (HPLC) methods for quantitative analysis. It is in this regard that two interlaboratory studies have been carried out in collaboration with Rhône-Poulenc Rorer. The first concerned the analysis of a single drug product (ketoprofen) and was typically a “simple analysis”. The second one involved a complex mixture of drug products and related substances (spiramycin), requiring far more constraining analysis conditions. Preliminary studies of the analyses were carried out to develop an optimized protocol. Statistical exploitation of the data for ketoprofen showed that there was no significant influence of the factors “laboratory” and “preparation”, under the conditions of the study. On the other hand, in the case of spiramycin, a significant influence of the factors “laboratory” and “preparation” was observed under the conditions of the collaborative study, indicating that the latter factor must be taken into account to establish certified assays. Results of these two studies will help to determine the factors that have a significant influence, depending on the product and the chromatographic method used. By completing the statistical data base, interlaboratory studies will also contribute in the near future to the elaboration of more rigorous protocols for analytical transfers.