Following the German‐Chinese Drug Screening Program, 86 racemic drugs were investigated in capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) hexakis‐(2,3,6‐tri‐O‐methyl)‐α‐cyclodextrin (TM‐α‐CD). Of the 86 drugs, 23 were separated into enantiomeric pairs. A comparison of the migration separation factors (αm) and the migration retardation factors (Rm) with previously published data for native α‐CD revealed that the ‘upper‐rim’ hydroxyl groups do not necessarily facilitate the recognition of the drug enantiomers by the chiral host. In contrast, an overall increase in affinity for the permethylated host led to a higher rate of successful enantiomer separations. A key substructure (4H) was identified in the analyte structure domain, with a crucial influence on the behavior of a particular drug.