Criteria for Developing Rugged High-performance Liquid-chromatographic Methods

An approach is described that allows the ultimate ruggedness of chromatographic methods to be rigorously included as an objective from the outset of systematic method development. Ruggedness criteria are defined as derivatives of other (typically resolution-based) criteria. Numerical estimates of ruggedness criteria can readily be obtained during selectivity optimization. It is necessary to consider ruggedness simultaneously with other objectives of the separation using multi-criteria decision making (MCDM) procedures. Three MCDM methods were considered in this work, viz., Pareto-optimality (PO) plot, Derringer's desirability function and the multiple threshold approach (MTA), The characteristics of these three methods are discussed and the feasibility of developing rugged separations by systematically varying the pH acid solvent composition is demonstrated.