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N O V E M B E R 1 , 2 0 0 1 / A N A LY T I C A L C H E M I S T R Y6 0 9 A o achieve high resolution and accurate peak integration, analytical chromatographers choose experimental conditions under which nonlinear effects are minimized. Careful use of these same effects allows them to design profitable separations.Nonlinear effects are ubiquitous. There are almost no experimental conditions under which they do not exist, although under many they are negligible. The key to understanding nonlinear effects lies in the equilibrium isotherms, the relationship between the solute concentrations at equilibrium in the two phases of the system. In most separations, particularly in chiral ones, the determination of these isotherms also allows more accurate investigation of the retention mechanism. We will show how band profiles can be modeled, why the model results are useful, and how systematic isotherm mea surements allow a deeper understanding of certain retention mechanisms.W Wh ha at t i is s n no on nl li in ne ea ar r c ch hr ro om ma at to og gr ra ap ph hy y? ?The goal of preparative chromatography is the rapid preparation of a significant amount of one component in a mixture to a sufficient degree of purity (1). Thus, large amounts of high-concentration samples are injected. Because of the finite surface area of the stationary phase in the column, the relative amount of a component adsorbed at equilibrium usually decreases as concentration increases, affecting retention. This phenomenon characterizes nonlinear chromatography.Peaks tail strongly in preparative chromatography, in contrast to the symmetrical peaks in analytical (i.e., linear) chromatography (2). Most often, nonlinear tailing peaks have sharp fronts and long, diffuse rear boundaries. The retention time of the high-concentration front decreases with increasing sample size, while the end of the peak tail has a con-