Precision of the reportable result. Simultaneous optimisation of number of preparations and injections for sample and reference standard in quantitative liquid chromatography

Abstract

In pharmaceutical analysis, the precision of the reportable result, i.e. the result which is to be compared to the specification limit, is relevant for the evaluation of the suitability of the analytical procedure. But also for other applications, the precision of the result is important and an optimisation often of interest. However, increasing the number of determinations (e.g. injections or preparations) will reduce only the variability (or standard error) of the corresponding precision level. Therefore, the knowledge of the individual variance contributions, obtained from reliable precision studies is important to determine on a scientific basis which format of the (reportable) result, i.e. the number of injections and sample preparations (or even series), should be used. In case of relative analytical procedures such as LC, the calibration model and format, i.e. the number of determinations of the reference standard is one of the factors (besides instrument, operator, reagents, etc.) affecting the between-series variance contribution at intermediate precision/reproducibility level. Consequently, the precision of the reportable result is only valid for the calibration format used to obtain intermediate precision/reproducibility. Instead of repeating the whole precision study to optimize the calibration format, the present paper describes a statistical approach using variability results from the original precision study