Chiral separation of beta-blocker drug nadolol by HPLC--a kinetic and equilibrium study

A Chiralpak AD-H column packed with amylose tris(3,5-dimethylphenylcarbamate) coated on silica gel was used to study the enantioseparation of nadolol by HPLC. 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 the solid film linear driving force model. The equilibrium constants were found to be 3.81, 5.24, 9.45 and 19.41 for the stereoisomers (SRS)-, (SRR)-, (RSS)- and (RSR)-nadolol, respectively. Their overall mass transfer coefficients were found to be 1841.8, 1254.8, 799.4 and 401.7 min(-1) respectively. Temperature effect on the enantiomeric separation and thermodynamic properties including enthalpy and entropy change of binding to the amylose tris(3,5-dimethylphenylcarbamate) stationary phase were also investigated. The moment analysis and the parameters obtained were used to simulate nadolol elution profiles. The simulated results matched the experimental profiles well, which confirmed the validity of model parameters obtained in this study.