Simultaneous enantioseparation with sensitive detection of four basic drugs, namely methoxamine, metaproterenol, terbutaline and carvedilol, using a 20-mu m ID capillary with native P-CD as the chiral selector was demonstrated by the large-volume sample stacking method. The procedure included conventional sample loading either hydrodynamically or electrokinetically at longer injection times without polarity switching and EOF manipulation. In comparison to conventional injections, depending on the analyte, about several hundred- and a thousand-fold sensitivity enhancement was achieved with the hydrodynamic and the electrokinetic injections, respectively. The simple method developed was applied to the analysis of racemic analytes in serum samples and better recovery was achieved using hydrodynamic injection than electrokinetic injection.