The aim of this study was to apply quality-by-design principles to build in a more scientific and risk-based multifactorial strategy in the development of an ultrahigh-pressure liquid chromatography (UHPLC) method for omeprazole and its related impurities.
Through the International Conference on Harmonization (ICH), this concept resulted in ICH guideline Q8(R2) in which quality-by-design is defined as "a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management" (3).
A systematic approach should replace the still common "screening", also known as a trial-and-error approach, in which one factor at a time (OFAT) is varied until the best method is found. The OFAT approach is time-consuming and often results in a nonrobust method because interactions between factors are not considered.
Today, systematic concepts use experimental design plans as an efficient and fast tool for method development. In a full or fractional factorial design, a couple of experiments are carried out in which one or more factors are changed at the same time. By using statistical software tools (for example, Design Expert from Stat-Ease, Inc.), the effect of each factor on the separation can be calculated and the data can be used to find the optimum separation (4). In our laboratory, this concept is used when the development of nonchromatographic methods is necessary.
However, the easiest and fastest way of developing a liquid chromatographic method is by using chromatography modelling, especially in combination with ultrahigh-pressure liquid chromatography (UHPLC) technology. Based on a small number of experiments, these software applications can predict the movement of peaks when parameters such as eluent composition or pH, flow rate, column temperature, column dimensions, and particle size are changed (5–11). When necessary, the developed method can be transferred (back) to high performance liquid chromatography (HPLC).