Estimation of the octanol-water distribution coefficient of basic compounds by a cationic microemulsion electrokinetic chromatography system

• Main Authors: Alejandro Fernández-Pumarega (Author), Belén Martín-Sanz (Author), Susana Amézqueta (Author), Elisabet Fuguet (Author), Martí Rosés (Author)
• Format: Book
• Published: International Association of Physical Chemists (IAPC), 2020-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1848-7718; 10.5599/admet.760
• Keywords: lipophilicity; log po/w; log do/w; meekc; ionized bases; solvation parameter model; microemulsion; system surrogation; Therapeutics. Pharmacology; RM1-950
• Source: ADMET and DMPK, Vol 8, Iss 1, Pp 98-112 (2020)

The octanol-water partition coefficient (Po/w), or the octanol-water distribution coefficient (Do/w) for ionized compounds, is a key parameter in the drug development process. In a previous work, this parameter was estimated through the retention factor measurements in a sodium dodecyl sulfate (SDS) - microemulsion electrokinetic chromatography (MEEKC) system for acidic compounds. Nonetheless, when ionized basic compounds were analyzed, undesirable ion pairs were formed with the anionic surfactant and avoided a good estimation of log Do/w. For this reason, an alternative MEEKC system based on a cationic surfactant has been evaluated to estimate Po/w or Do/w of neutral compounds and ionized bases. To this end, it has been characterized through the solvation parameter model (SPM) and compared to the octanol-water partition system. Results pointed out that both systems show a similar partition behavior. Hence, the log Po/w of a set of neutral compounds has been successfully correlated against the logarithm of the retention factor (log k) determined in this MEEKC system. Then, the log Do/w of 6 model bases have been estimated at different pH values and they have been compared to data from the literature, determined by the reference shake-flask and potentiometric methods. Good agreement has been observed between the literature and the estimated values when the base is neutral or partially ionized (up to 99 % of ionization).