USE OF OVERLAPPING RESOLUTION MAPPING SCHEME FOR OPTIMIZATION OF THE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC SEPARATION OF PHARMACEUTICALS

The use of overlapping resolution mapping (ORM) for the optimization o f HPLC separations was examined. The ORM scheme was employed to predic t the optimum conditions required for the isocratic HPLC separation of a group of basic pharmaceuticals. The ORM scheme involved first perfo rming seven pre-planned experiments located on a triangle representing the mobile phase compositions. From these experiments, and through th e use of a Basic program, the optimum conditions required for separati on-were established. The scheme was initially applied to establish the optimum mobile phase compositions consisting of quaternary mixtures o f buffered acetonitrile, methanol and 2-propanol with a C-18 column. T his approach was found to offer a very rapid and versatile means of de termining the optimum HPLC conditions required for such a complex mobi le phase system. Complete separation of all the peaks in the mixture w as achieved using a mobile phase composition of acetonitrile-methanol- 2-propanol-buffer (50:15:5:30, v/v) derived from the ORM scheme. The u sefulness and versatility of the ORM scheme was further demonstrated t hrough the use of the optimum mobile phase compositions with different C-18 columns. It was found that satisfactory separation was achieved by adopting the established optimum mobile phase composition without t he need to perform any further re-optimization. In addition, the preci sion, selectivity and linearity of the method developed were found to be highly reproducible and reliable.