A three-factor optimisation strategy for micellar liquid chromatography

An interpretive optimisation methodology for micellar liquid chromatography (MLC) is shown, taking into account pH, surfactant (sodium dodecyl sulphat e) and organic modifier (propanol) concentrations. Two objectives are consi dered: to develop a highly practical straightforward three-factor optimisat ion for practical MLC, and, in order to avoid unecessary experiments, to li nk two and three-factor optimisations through a stepwise construction of th e experimental design at different pH levels. The whole pH range for an ODS column (from 3 to 7) is covered. The proposed strategy was thoroughly eval uated using the chromatographic data from 81 experimental mobile phases, ap plied to the separation of a set of solutes exhibiting diverse acid-base be haviour where some of them had partial proto nation which is difficult to m odel. When all the available information was used for modelling the system, the global mean error in the prediction of the retention was 2.5%. When le ss information was used to achieve a practical number of experiments, the e rrors increased and depended on the experimental design. A basic design con sisting of a 3 x 2(2) (pH, surfactant, modifier) regular distribution of ex periments gave good descriptions, except for those solutes with a partial p rotonation in the studied pH range. The mean error obtained using a 3 x 2(2 ) + 3 learning set (15 experiments) and a test set of 66 experiments was 4% . A final strategy is proposed which has the advantage of allowing partial optimisations in two factors at constant pH levels, before completing the t hree-factor experimental design. The sequential strategy adapts retention m odel and design to the difficulty of the separation problem, which saves fu rther experimental work if any of the developed partial optimisations succe eds before developing the three factor design. In a favourable case, four e xperiments can be enough.