Robustness testing of a liquid chromatography method for the determination of vorozole and its related compounds in oral tablets

The robustness of a method for the determination of vorozole in oral tablets was examined by applying a two-level, seven factor Plackett-Burman statistical experimental design. Five method variables that are sensitive to variation, especially during method transfer, were evaluated for their influence on the system suitability criteria set in the method procedure and on the analysis time. The method variables were investigated in a specified range above and below the nominal method conditions. They included the concentration of an ion-pairing agent, the percentage organic modifier at the start of the linear gradient, the mobile phase Bow rate, the percentage organic modifier at the end of the linear gradient and the pH of the mobile phase. Two dummy factors were included in the design to estimate the experimental error. It was found that none of the five studied variables affected significantly (t-test, alpha = 0.01) the capacity factor, the tailing factor or the analysis time. The resolution of the critical peak: pair on the other hand, was significantly influenced by the factor pH. However, the responses for the resolution of all the experimental runs in the design were well above the system suitability limit stated in the normal assay procedure. Therefore, the method can overall be considered robust. (C) 1998 Elsevier Science B.V. All rights reserved.