Efficient applications of capillary electrophoresis-tandem mass spectrometry to the analysis of adrenoreceptor antagonist enantiomers using a partialfilling technique

Throughout the separation of chiral basic drugs by capillary electrophoresi s (CE) with neutral hydroxypropyl-beta -pcyclodextrin (HP-beta -CD) as chir al selector, the sensitivity of detection can be improved by using tandem m ass spectrometric (MS-MS) detection with a partial filling technique rather than with UV spectrometric detection. Prior to sample injection, the capil lary was partly filled with HP-beta -CD dissolved in volatile ammonium form ate buffer (pH 4, ionic strength 50 mM). The effects of modifying the HP-be ta -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-m olecular MH+ ion were investigated. For a given selector zone length, as th e concentration of the neutral cyclodextrin increases, the resolution betwe en enantiomers becomes higher (the opposite of the behavior of the signal-t o-noise ratio) and then reaches an optimum value. The decrease of the selec tor zone length lowered the resolution between the enantiomers but increase d peak efficiencies and signal-to-noise ratio values. Accordingly, partial capillary filling at 80% (v/v) and 10 mM concentration of HP-beta -CD was s elected as a suitable compromise between resolution and sensitivity of MS d etection. Limits of detection for each adrenoreceptor antagonist enantiomer were 5 ng/ml (0.02 muM) in CE-MS-MS instead of 150 ng/ml (0.60 muM) in CE- UV, which enhances sensitivity by a factor of 30. (C) 2001 Elsevier Science B.V. All rights reserved.