Throughout the separation of chiral basic drugs by capillary electrophoresis (CE) with neutral hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector, the sensitivity of detection can be improved by using tandem mass spectrometric (MS-MS) detection with a partial filling technique rather than with UV spectrometric detection. Prior to sample injection, the capillary was partly filled with HP-β-CD dissolved in volatile ammonium formate buffer (pH 4, ionic strength 50 mM). The effects of modifying the HP-β-CD concentration in the selector zone and the length of the separation zone on the enantioresolution and the signal-to-noise ratio of the pseudo-molecular MH + ion were investigated. For a given selector zone length, as the concentration of the neutral cyclodextrin increases, the resolution between enantiomers becomes higher (the opposite of the behavior of the signal-to-noise ratio) and then reaches an optimum value. The decrease of the selector zone length lowered the resolution between the enantiomers but increased peak efficiencies and signal-to-noise ratio values. Accordingly, partial capillary filling at 80% (v/v) and 10 mM concentration of HP-β-CD was selected as a suitable compromise between resolution and sensitivity of MS detection. Limits of detection for each adrenoreceptor antagonist enantiomer were 5 ng/ml (0.02 μM) in CE-MS-MS instead of 150 ng/ml (0.60 μM) in CE-UV, which enhances sensitivity by a factor of 30.