ADMET and DMPK, Vol. 8 No. 1, 2020.
Izvorni znanstveni članak
https://doi.org/10.5599/admet.760
Estimation of the octanol-water distribution coefficient of basic compounds by a cationic microemulsion electrokinetic chromatography system
Alejandro Fernández-Pumarega
; Departament d’Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain
Belén Martín-Sanz
; Departament d’Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain
Susana Amézqueta
orcid.org/0000-0001-8976-467X
; Departament d’Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain
Elisabet Fuguet
; Departament d’Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain
Marti Rosés
; Departament d’Enginyeria Química i Química Analítica and Institut de Biomedicina (IBUB), Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain
Sažetak
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).
Ključne riječi
Lipophilicity; log Po/w; log Do/w; MEEKC; ionized bases; solvation parameter model; microemulsion; system surrogation
Hrčak ID:
235015
URI
Datum izdavanja:
4.3.2020.
Posjeta: 744 *