The formation of hydrates of inorganic compounds is well known and is widely discussed in the contemporary literature. The reasons for the insufficiently detailed characterization of numerous well-known hydrates of organic compounds are analyzed, the main of which is their instability. The CAS numbers assigned to many of these hydrates confirm interest in these hydrates. We found that the reversible formation of the hydrates of various organic compounds can be a reason for anomalous dependences of their retention parameters (tR) on the concentration of an organic eluent modifier (c) in reversed-phase high-performance liquid chromatography. The recurrent approximation of the retention parameters tR(c + Δc) = atR(c) + b (*), where Δc = const is a constant step of c, is the most effective way to detect these anomalies. Deviations of dependences like (*) from linearity are observed with compounds in which variations in c and, consequently, in the water content of the eluent (1 – c) affect the equilibrium of the reaction $${\text{X}} + n{{{\text{H}}}_{{\text{2}}}}{\text{O }} \rightleftarrows {\text{X}} \cdot n{{{\text{H}}}_{{\text{2}}}}{\text{O}}.$$