Investigation of the limitations of saturated fractional factorial experimental designs,with confounding effects for an HPLC ruggedness test

Summary Recently much attention has been directed to the validation of analytical methods. The level of validation will depend on the method application. If a method is developed for general use, for instance by different analysts, instruments or laboratories, then the effect of these changes need evaluation. This is normally referred to as ruggedness testing, where the limitations of the method to changes in the specified conditions are examined.This paper examines the use of Plackett-Burman fractional factorial experiment designs for ruggedness testing in high performance liquid chromatography (HPLC). The ability of these designs to identify confounding effects is applied to the stability indicating analysis of Salbutamol and its major degradation product, AH4045. The results show that confounding effects, proving extremely pertinent to HPLC, can be identified.The assay proved rugged to most tested changes although not to the use of column packing material from different manufacturers.