A small series of steroid hormones and synthetic steroid anabolics, eluted from a sample by using classical methanol-water mobile phase, was designed at molecular level with in vitro geometrical modeling. Structure-based properties of the compounds were extracted for different strategies of geometry optimization and were related with the percent retardation factors observed in the experiment by using classical linear regression approach. The obtained models were assessed and the most accurate model was selected. The obtained relationship between the structure and retardation factor was interpreted in order to express the main factors driving liquid phase mobility of compounds as a function of their structure. The analysis allowed a series of general conclusions regarding the modeled property (percent of retardation factor), modeling strategy (with help of a family of molecular descriptors) as well as about the level of theory in geometrical modeling (Ab-initio 6-31G*, CLHF, core Hamiltonian guess, symmetr...