Parametric Modulation in Liquid Chromatography:  Multivariate Optimization of Mobile Phase Composition and Temperature

Abstract

The concept and theory of parametric modulation are presented, and the strategy is demonstrated for multivariate optimization of mobile phase composition and temperature in liquid chromatography. Because each parameter to be optimized is maintained in separate and distinct zones along the column, the solutes are able to interact independently within each environment. Under these conditions, solute retention is a simple and rigorously predictable summation of the retention in each environment. Hence, parametric modulation is more accurate and requires fewer preliminary experiments than traditional optimization methods. This approach is demonstrated by application to the separation of isomeric polynuclear aromatic hydrocarbons using a polymeric octadecylsilica stationary phase, with methanol and acetonitrile mobile phases at temperatures from 23 to 45 °C.