Liquid chromatography (LC) and capillary electrophoresis (CE) are very widely used as chiral separation methods. In this publication we try to find if the results obtained in CE and LC with the chiral selector added to the electrolyte and the mobile phase, respectively, can be used as tools for studying weak stereoselective interactions, and how this information can be useful for optimizing chiral separation processes. The manuscript presents a systematic comparison of chiral discrimination of model compounds in HPLC and CE using neutral and negatively charged cyclodextrins. The enantiomeric separation of basic chiral pharmaceuticals such as pheniramine, brompheniramine, metoxyphenamine, cyclopentolate, doxylamine and ketamine was investigated in capillary electrophoresis (CE) and liquid chromatography (HPLC) using negatively charged sulfated-beta-cyclodextrin (S-beta-CD) and neutral cyclodextrins (CDs). The apparent stability constants between the model compounds and cyclodextrins were estimated in both techniques. We discuss the influence of the stability constant and K1/K2 ratio of the investigated complexes on chiral separation obtained in both techniques.