When pH is used as factor in reversed-phase liquid chromatographic (RPLC) separations, the need for providing quality and informative data with the minimal experimental effort becomes imperative. The most rational way to achieve this is by means of experimental designs. The interest in finding optimal designs involving solvent content and pH in RPLC is considerable, since these factors allow large variations in selectivity when ionisable compounds are involved. Unfortunately, the equations that describe the retention of these compounds with pH are nonlinear. As a consequence, factorial and other designs based on geometrical considerations are not well suited, whereas D-optimal and related designs can only be applied in an iterative fashion. In this work, an extension of G-optimal designs, aimed to enhance the quality of the predictions, is examined for problems involving solvent content and pH. The study was carried out with a set of probe ionisable compounds, for which information on retention behaviour was accurately known. A stepwise strategy was used to obtain a rapid estimation of the best design with a given number of experiments. The objective of the study was to investigate the distribution and number of points in the ideal design for compounds of different acid-base behaviour, and the possibility of finding common designs for groups of compounds. A further goal was to derive design construction rules containing the information requirements, without needing any further mathematical treatment.