Strategy for ruggedness tests in chromatographic method validation

The search for sources from which small changes have an in ̄uence on the response of an analytical system, the ruggedness test, has become an essential part of a validation study. However, the `de®nition' of ruggedness and how to perform a ruggedness test are still ambiguous. In this paper a strategy is proposed to perform a ruggedness test for chromatographic methods. Because the strategy is based on saturated designs, ANOVA cannot be applied to estimate the error variance. Therefore a graphical technique, the half-normal plot, is used to detect in ̄uential effects. In order to identify in ̄uential effects, the algorithms of Lenth and Dong are applied to four different examples. If a main effect is found to be signi®cant, the confounded two-factor interactions are resolved by a follow-up design. The strategy of this sequential design is implemented in a SAS software application called TRIC, testing ruggedness in chromatography. # 1999 Elsevier Science B.V. All rights reserved.