Kinetic and equilibrium study of the separation of three chiral center drug, nadolol, by HPLC on a novel perphenyl carbamoylated β-cyclodextrin bonded chiral stationary phase

Abstract

A column packed with novel perphenyl carbamoylated β-cyclodextrin (β-CD) immobilized onto silica gel was used to separate nadolol by high performance liquid chromatography. Resolution of three of the four stereoisomers of nadolol was obtained by the complete separation of the most active enantiomer (RSR)-nadolol in reversed phase. The optimum separation condition for the mobile phase contained 80% buffer solution (1% TEAA, pH 5.5) and 20% methanol. The bed voidage, axial dispersion coefficient, overall mass transfer coefficients as well as equilibrium constants for the chromatographic enantiomeric separation were evaluated by moment analysis on the basis of solid film linear driving force model. The equilibrium constants were found to be 2.94, 3.46, and 5.45 for the (SRS)- and (SSR)-nadolol, (RRS)-nadolol, and (RSR)-nadolol, respectively. Their overall mass transfer coefficients were found to be 669.3, 846.3, and 106.4 min-1, respectively. The simulated results matched the experimental profiles quite well, which confirmed the validity of model parameters obtained in this study.