Interlaboratory studies: the best way to estimate the characteristics of dispersion of an HPLC method and a powerful tool for analytical transfers

The characteristics of dispersion of an analytical method are required in each method validation. In spite (or because?) of technical progress, which has enabled full automation of the whole analysis, differences are often observed between repeatability and reproducibility. The only rigorous way to estimate reproducibility is the implementation of an interlaboratory study. The most appropriate technique used for data evaluation is the analysis of variance (ANOVA). It is thus possible to identify each significant source of variation of the method and to give an estimate of its corresponding dispersion. Moreover interlaboratory studies not only give information about fidelity but they also provide reference materials, the assay of which is certified. As an illustration we will present the results of two collaborative studies carried out on HPLC quantitative analysis of pharmaceutical drug products: ketoprofen(R) and spiramycin(R). Analytical transfers are an important concern today. As no actual guidelines are currently available, we decided to devise a rigorous methodology based on a statistic exploitation of results. The criteria of the transfer validation could be formulated as follows: "For each response of interest, the new laboratory must have dispersion characteristics compatible with those of the reference entity and must exhibit no bias". While compatibility of precision can be assessed easily, the test of absence of bias requires that certified materials be available. Since certified materials can only be obtained through an inter-laboratory study, it means that the reference entity is only available from a pool of laboratories.