Use of overlapping resolution mapping scheme for optimization of the high-performance liquid chromatographic separation of pharmaceuticals

Abstract

The use of overlapping resolution mapping (ORM) for the optimization of HPLC separations was examined. The ORM scheme was employed to predict the optimum conditions required for the isocratic HPLC separation of a group of basic pharmaceuticals. The ORM scheme involved first performing seven pre-planned experiments located on a triangle representing the mobile phase compositions. From these experiments, and through the use of a Basic program, the optimum conditions required for separation were established. The scheme was initially applied to establish the optimum mobile phase compositions consisting of quaternary mixtures of buffered acetonitrile, methanol and 2-propanol with a C18 column. This approach was found to offer a very rapid and versatile means of determining the optimum HPLC conditions required for such a complex mobile phase system. Complete separation of all the peaks in the mixture was achieved using a mobile phase composition of acetonitrile-methanol-2-propanol-buffer (50:15:5:30, v/v) derived from the ORM scheme. The usefulness and versatility of the ORM scheme was further demonstrated through the use of the optimum mobile phase compositions with different C18 columns. It was found that satisfactory separation was achieved by adopting the established optimum mobile phase composition without the need to perform any further re-optimization. In addition, the precision, selectivity and linearity of the method developed were found to be highly reproducible and reliable. © 1995.