COMPARISON OF THEORY-BASED AND EMPIRICAL MODELING FOR THE PREDICTION OF CHROMATOGRAPHIC BEHAVIOR IN THE ION-PAIRING SEPARATION OF BENZODIAZEPINE-DERIVED PHARMACEUTICAL COMPOUNDS

Two approaches were examined for predicting chromatographic behavior d uring the reversed-phase ion-pairing separation of benzodiazepine-deri ved pharmaceutical compounds. The capacity factor for olanzapine and i ts resolution from a closely related compound, desmethylolanzapine, we re studied as a function of the percentage of acetonitrile, the ion-pa iring reagent concentration and the buffer pH. In the first approach, the results were analyzed using the theory-based software package DryL ab I/mp. In the second approach, statistical analysis was used to deri ve empirical equations to predict the dependence of the chromatographi c behavior on each of the experimental variables. At the lowest ion-pa iring reagent concentration, DryLab I/mp was found to be a poor predic tor of resolution. For this complex separation, the empirical equation s derived from the statistical analysis were found to predict better t he chromatographic behavior over the ranges tested. These equations we re used to generate response-surface plots to evaluate the method rugg edness.