Full and fractionated experimental designs for robustness testing in the high-performance liquid chromatographic analysis of codeine phosphate, pseudoephedrine hydrochloride and chlorpheniramine maleate in a pharmaceutical preparation

This paper describes the testing of a saturated factorial design using a fu ll factorial design. Saturated factorial designs are often used to test the robustness of high-performance liquid chromatography (HPLC) methods, howev er they are based on several assumptions. A full factorial design relies on fewer assumptions and hence could be used to evaluate the effectiveness of the saturated design. Both designs were used to test a gradient HPLC metho d for the assay of codeine phosphate, pseudoephedrine hydrochloride and cho rpheniramine maleate. Six HPLC conditions, including wavelength, mobile pha se pH and ion pairing reagent concentration were tested using the saturated design. Three of these factors were selected for full evaluation using a f ull factorial design. The results showed that the main effects calculated b y each design were comparable. However, the saturated design showed higher standard errors, probably due to the effects of changing several more facto rs. One interaction effect was indicated as a confounding effect by the sat urated design and this was confirmed by the calculation of the same interac tion effect using the full design. Overall the method was shown to be robus t under the variety of HPLC conditions tested. (C) 2000 Elsevier Science B. V. All rights reserved.