Investigation of the retention mechanism of abiraterone and its metabolites on ODS stationary phases using computational chemistry.

Retention mechanisms of abiraterone (Abi, Abi1) and its metabolites [Δ4-Abi (D4A, Ab2), 3-keto-5α-Abi (Abi3), 3β-OH-5α-Abi (Abi4), 3α-OH-5α-Abi (Abi5), 3-keto-5β-Abi (Abi6), 3β-OH-5β-Abi (Abi7), 3α-OH-5β-Abi (Abi8) and 3α-OH-Abi (Abi9) on monomeric and polymeric ODS stationary phases were investigated using computational chemistry. Abi1/Abi9, Abi4/Abi5, Abi7/Abi8 and Abi3/Abi6 are pairs of diastereomers. The 1,3-diaxial interactions involving the C3‑hydroxy groups in Abi9, Abi5 and Abi8 appear to hinder hydration, leading to less favorable solvation and greater hydrophobicity than their corresponding diastereomers. Therefore, on monomeric ODS stationary phases, the elution orders were Abi1 < Abi9, Abi4 < Abi5, Abi7 < Abi8 and Abi3 ≈ Abi6, in agreement with the corresponding order of hydrophobicity. In contrast, on polymeric ODS stationary phases, the elution orders were Abi9 < Abi1, Abi5 < Abi4, Abi8 < Abi7 and Abi6 < Abi3. This reversal is likely attributable to the planarity recognition capability of the polymeric ODS stationary phase. On monomeric ODS stationary phases, the van der Waals interaction energies between Abi and its eight metabolites (Abi2 - Abi9) and the monomeric C12 stationary phase, calculated using the MM2 force field, showed a good correlation with their log k values. Furthermore, for six compounds bearing a C3‑hydroxyl group (Abi1/Abi9, Abi4/Abi5 and Abi7/Abi8), the hydration free energies calculated by the DFT/SMD method also showed a good correlation with their log k values.