Evolution from univariate to multivariate optimization methods in liquid chromatography

The rational evolution of optimization methods, from univariate to multivariate, is described together with selected examples of their application. A novel approach, parametric modulation, is then proposed which overcomes many limitations of the present methods. In this approach, each mobile phase, stationary phase, temperature, etc. to be optimized is maintained in discrete and separate zones along the column. The overall retention is a rigorously predictable function of the retention time in each individual environment. Hence, complete multivariate optimization can be achieved with good accuracy using a minimum number of preliminary experiments.