Optimization of the chiral resolution of four hydrophobic amines on CHIRAL-AGP by a central composite face design (CCF)

A three-factor central composite face design (CCF) has been used for the optimization of the chiral resolution of the enantiomers of alprenolol, oxprenolol, trimipramine and propranolol on CHIRAL-AGP. The variables (factors) investigated were pH and concentrations of the micellar agent Tween^® 20 and heptanoic acid. The responses evaluated were resolution (R_S), capacity factor (k) of the last eluted enantiomer and a chromatographic response function (CRF) defined as CRF = P⁵/log t_ret, where P is the peak-valley ratio according to Kaiser and t_ret is the retention time. The computed models, one for each substance and one for each response (in total 12 models), showed that the main factor for the regulation of R_S as well as k and CRF in the experimental domain is the pH. The optimal pH for the substances could be found between pH 5.5 and 6.5. The optimum was evaluated by generating contour plots for the CRF models. The computed mathematical models were statistically evaluated and the predictive power of the models was tested by experimentation.Dedicated to Professor Dr. Dr. h.c. mult. J.F.K. Huber on the occasion of his 70th birthday