Protein-based chiral stationary phases, in particular α(1)-acid glycoprotein, are chromatographic materials with a very broad application range. The chiral recognition ability of this selector allows the resolution of more than 90% of the molecules tested. A step-by-step description of the screening approach that we have developed is described in this article with two objectives in mind: obtaining a high success rate with a straightforward methodology that can be generally applied and allowing LC-MS compatibility. Second, the screening strategy is required to take into account the main functional nature of the racemic compound to be resolved (neutral, acidic or basic) for method optimisation step, but should be independent of other structural features, in order to allow the routine application of screening sequences and the application to the largest number of samples.