The structure of drug compounds is relatively complex, and it is difficult to predict their elution behavior. The figure above shows an example of the same substance having different retention behavior depending on the surface structure of the stationary phase. Unison "Unison" series is compatible with 100% aqueous eluents and is designed with excellent retention and separation characteristics for highly polar compounds. On the other hand, Cadenza CD-C18 is designed as a stationary phase with a relatively high ligand density of ODS (octadecyl group) and enhanced molecular recognition of the steric different compounds.
The following differences among stationary phases are observed regarding the retention behavior of pravastatin (a hyperlipidemia therapeutic drug) shown above.

Among the Unison series, the order of retention is Phenyl < C8 < C18

In general, the hydrophobicity of the reversed-phase (RP) stationary phase increases with the length of the alkyl chain. Unison's RP phases have been designed based on this concept, leading to the observed elution behavior. The Phenyl stationary phase has a carbon number of C6, but the presence of pi electrons derived from benzene slightly increases the polarity of the stationary phase, making it similar to C4.

Even with the same ODS, Unison UK-C18 has greater retention than Cadenza CD-C18.

The ODS ligand density of Unison UK-C18 is lower than that of Cadenza CD-C18. Therefore, if considering hydrophobicity alone, the solute retention should be shorter on Unison. However, Unison exhibits greater retention of pravastatin than Cadenza, and several reasons could explain this phenomenon:

First, the solute's structure contains many oxygen atoms. As such, the solute is likely to exhibit strong electrostatic interactions due to dipole moments caused by the electron lone pairs in the oxygen atoms and hydrogen bonds derived from hydroxyl groups.

Second, the Unison stationary phase's surface features a siloxane structure with oxygen atoms, which could result in hydrogen bonding or dipole-dipole interactions (i.e., electrostatic interactions) with the solute.

Finally, even though Cadenza and Unison use the same ODS, Cadenza's high ligand density could prevent the solute from getting close to the silica surface, thereby reducing these interactions. As a result, Unison might exhibit greater retention than Cadenza due to increased electrostatic interactions near the silica substrate surface.

As mentioned in the previous section, since Cadenza has a high ODS density, it is believed that electrostatic interactions near the silica surface are not as prominent. Since C8 has a much shorter alkyl chain length than ODS (C18), it is conjectured that the solute can reach closer to the substrate surface. The magnitude of the interaction can be summarized as follows.

Comparison of ODS Retention Characteristics for Polar Compounds