Comparison of several criteria to decide on the significance of effects in a robustness test with an asymmetrical factorial design

A robustness test was performed for the reversed-phase HPLC method to determine the total content of triadimenol. It is based on an asymmetrical factorial design that allows examination of simultaneously a factor (column manufacturer) at four levels and 12 factors at two levels. Different error estimates applied in a t-test statistic to decide on the significance of the factor effects were compared. Dummy factor effects and experiments at the nominal level of the quantitative factors were used to derive critical effects. Moreover, methods that estimate the critical effects from the distribution of the non-significant effects were also applied. These statistical methods are compared with a graphical evaluation by means of the half-normal plot.

[1]  D. L. Massart,et al.  Ruggedness tests on the high-performance liquid chromatography assay of the United States Pharmacopeia xxii for tetracycline hydrochloride - a comparison of experimental-designs and statistical interpretations , 1995 .

[2]  D L Massart,et al.  A ruggedness test strategy for procedure related factors: experimental set-up and interpretation. , 1998, Journal of pharmaceutical and biomedical analysis.

[3]  S. Addelman Orthogonal Main-Effect Plans for Asymmetrical Factorial Experiments , 1962 .

[4]  Frederick Mosteller,et al.  Data Analysis and Regression , 1978 .

[5]  F. A. Maris,et al.  Ruggedness testing of gas chromatographic method for residual solvents in pharmaceutical substances , 1994 .

[6]  D L Massart,et al.  RTS, a computer program for the experimental set-up and interpretation of ruggedness tests. , 1998, Journal of pharmaceutical and biomedical analysis.

[7]  M. Mulholland,et al.  Investigation of the limitations of saturated fractional factorial experimental designs, with confounding effects for an HPLC ruggedness test , 1988 .

[8]  R. Plackett,et al.  THE DESIGN OF OPTIMUM MULTIFACTORIAL EXPERIMENTS , 1946 .

[9]  C. Daniel Use of Half-Normal Plots in Interpreting Factorial Two-Level Experiments , 1959 .

[10]  D. L. Massart,et al.  Ruggedness tests for a high-performance liquid Chromatographic assay: Comparison of an evaluation at two and three levels by using two-level Plackett-Burman designs , 1995 .

[11]  Lutgarde M. C. Buydens,et al.  RES, AN EXPERT SYSTEM FOR THE SET-UP AND INTERPRETATION OF A RUGGEDNESS TEST IN HPLC METHOD VALIDATION .1. THE RUGGEDNESS TEST IN HPLC METHOD VALIDATION , 1991 .

[12]  R. Lenth Quick and easy analysis of unreplicated factorials , 1989 .