Total chromatographic optimization (TOCO) I. Simultaneous optimization of many variables in liquid chromatography

Summary The following chromatographic variables are totally optimized based on the recently developed information theory of optimization: mobile phase composition, column length, flow rate, wavelength, and the amount of internal standard. The optimal internal standard is selected from among six candidates. Two types of optimal conditions (- and -optimals) are proposed: the -optimal is defined as the most precise analysis (the maximal ) while the -optimal is the most efficient (rapid) analysis (the maximal ). The observation times for the determination of an antipyretics mixture (three components) in liquid chromatography are ca. 50 s for the -optimal and ca. 8 min for the -optimal. The reliability of the - and -optimals is verified by experiments.