Strategy for ruggedness tests in chromatographic method validation

The search for sources from which small changes have an influence on the re sponse of an analytical system, the ruggedness test, has become an essentia l part of a validation study. However, the 'definition' of ruggedness and h ow to perform a ruggedness test are still ambiguous. In this paper a strate gy is proposed to perform a ruggedness test for chromatographic methods. Be cause the strategy is based on saturated designs, ANOVA cannot be applied t o estimate the error variance. Therefore a graphical technique, the half-no rmal plot, is used to detect influential effects. In order to identify infl uential effects, the algorithms of Lenth and Dong are applied to four diffe rent examples. If a main effect is found to be significant, the confounded two-factor interactions are resolved by a follow-up design. The strategy of this sequential design is implemented in a sas(R) software application cal led TRIC, testing ruggedness in chromatography. (C) 1999 Elsevier Science B .V. All rights reserved.