Abstract: Five antitumor drugs are selected as examples of polyfunctional organic compounds to test the possibilities of approximating their retention parameters in reversed-phase high-performance liquid chromatography using recurrent relationships of the form of t _R(C + ΔС) = at _R(C) + b, where C is the concentration of organic modifier in the composition of the eluent (acetonitrile), ΔC = const is a constant step of its change in concentration, and a and b are coefficients calculated using the least squares method. Examples of both ideally linear dependences in all ranges of acetonitrile concentrations and deviations from linearity in different ranges of its concentrations are revealed. Discussion of the possible reasons for such deviations (both structural factors and physicochemical properties) suggests that acid–base equilibria in the eluent are not the main ones, the positions of which depend on the concentration of the organic component. The reversible formation of hydrated forms typical of compounds whose molecules contain such polar fragments as amide ‒CO–NH– and sulfonamide –SO ₂–NH groups, seems more likely. Recurrent approximation of the retention parameters can be considered the simplest and most obvious way to reveal the specific interactions of the test compounds with components of the eluent.