Some organic compounds form hydrates in eluents under the conditions of reversed-phase high-performance liquid chromatography (RP HPLC). For some of them, variation of water to the organic solvent ratio in an eluent may influence the ratio of hydrated and non-hydrated forms of analytes, X + nH2O ⇄ X·nH2O, which complicates the relations of their chromatographic retention. To reveal the formation of such hydrates, the recurrent approximation of their retention parameters is recommended, tR(C + ΔC) = atR(C) + b (*), where ΔC = const is the concentration increment of an organic modifier in an eluent, and a and b are coefficients calculated by the least-squares method. If an analyte exists in a hydrated or non-hydrated form only, the correlation coefficients (R) of equation (*) exceed 0.999. If the reversible formation of hydrates takes place within the concentration range Cmin to Cmax, it leads to distortion of linear dependence (*) and to deviations of some data points from regression lines (R < 0.999). One of the structural factors responsible for the reversible formation of hydrates is the presence of polar sulfonamide group –SO2NRR' in a molecule. To confirm this, a series of N-substituted p-toluenesulfonamides were synthesized and characterized. However, the nonlinearity of recurrences (*) is observed only for acetonitrile-containing eluents.