EFFECT OF CHARGED AND UNCHARGED CHIRAL ADDITIVES ON THE RESOLUTION OFAMLODIPINE ENANTIOMERS IN LIQUID-CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS

Neutral cyclodextrins (CDs) and derivatives carrying an overall cation ic or anionic charge are widely utilised as chiral additives in liquid chromatography (LC) and particularly in capillary electrophoresis (CE ). Five neutral CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-C D (HP-beta-CD) and hydroxyethyl-beta-CD (HE-beta-CD)) and the anionic sulphobutylether-beta-CD (SBE-beta-CD) and carboxymethyl-beta-CD (CM-b eta-CD) have been examined for the resolution of amlodipine enantiomer s both in LC and in CE. In LC, although the neutral CDs yielded no ena ntioselectivity for amlodipine, CM-P-CD did show enantioselectivity (R -s=1.1, t(R)=35 min), albeit with poor peak shape. It was found, howev er, that the anionic SBE-beta-CD gives a robust separation (R-s=1.7, t (R2)=21.5 min) when using acetonitrile-20 mM NaH2PO4 (pH 3.95), contai ning 20 mM SBE-beta-CD (35:100, v/v). A spectrophotometric continuous- variation plot method was used to determine that the amlodipine-SBE-be ta-CD complex has predominantly a 1:1 stoichiometry in solution. Stabi lity constants have been calculated for this 1:1 complex in LC. For ea ch amlodipine enantiomer with the anionic SBE-beta-CD, these were 596 and 561 M-1, respectively. The enantiomers of amlodipine are also sepa rated in CE using hydroxypropyl-beta-CD (20 mM) and the anionic SBE-be ta-CD (1 mM) and CM-beta-CD (2.5 mM) where the anionic CDs were shown to offer an enhanced enantioselectivity over the neutral CD. The amlod ipine enantiomer migration order in CE is found to be the same for bot h anionic and neutral CDs. Further examination of the enantiomer migra tion order indicated that the binding constant for the S enantiomer to the SBE-beta-CD was greater than that for the corresponding R enantio mer. It was then possible, by examining the enantiomer retention, to c onclude that in LC the enantioselective interaction between each amlod ipine enantiomer and the anionic SBE-beta-CD occurs in the bulk mobile phase and not on a dynamically coated chiral stationary phase. (C) 19 98 Elsevier Science B.V.