Development and evaluation of a linear regression method for the prediction of maximal chiral separation of basic drug racemates by cyclodextrin-mediated capillary zone electrophoresis.
An important step in method development of chiral separations with neutral cyclodextrins (CDs) as chiral selectors is the estimation of the CD concentration that gives the highest degree of separation. From the equation [S]opt=1/(K1K2)(1/2) this optimal CD concentration can be calculated if any knowledge is available about the binding constants K1 and K2 of both enantiomer complexes. These values can be obtained by measuring the effective velocities of each enantiomer as a function of the selector concentration and fitting these profiles by non-linear least-square regression. An alternative approach has been developed which makes it possible to predict the optimal CD concentration from a few experiments performed at low CD concentrations. The model is developed using some antimycotic imidazole derivatives (econazole, miconazole and isoconazole) as test substances and hydroxypropyl-beta-CD as chiral selector. The results obtained by this method are in good agreement with those from non-linear least-square regression.
Van Eeckhaut
A
A
Department of Pharmaceutical Chemistry and Drug Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel, Brussels, Belgium.
Boonkerd
S
S
Detaevernier
M R
MR
Michotte
Y
Y
D003505:Cyclodextrins / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D016014:Linear Models; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism
D003505:Cyclodextrins; D004364:Pharmaceutical Preparations