The process of developing new reversed-phase liquid chromatography methods can be both time-consuming and challenging. To meet this challenge, statistics-based strategies have emerged as cost-effective, efficient and flexible solutions. In the present study, we use a Bayesian response surface methodology, which takes advantage of the knowledge of the pKa values of the compounds present in the analyzed sample to model their retention behavior. A multi-criteria decision analysis (MCDA) was then developed to exploit the uncertainty information inherent in the model distributions. This strategic approach is designed to integrate seamlessly with quantitative structure retention relationship (QSRR) models, forming an initial in-silico screening phase. Of the two methods presented for MCDA, one showed promising results. The method development process was carried out with the optimization phase, generating a design space that corroborates the results of the selection phase.