Abstract
Previous studies have shown that a microemulsion electrokinetic chromatography (MEEKC) system can estimate the logarithm of the octanol-water partition coefficient (log P<sub>o/w</sub>) of neutral solutes. In the present work, the applicability of the method to partially and fully ionized acids has been evaluated. Naproxen, a monoprotic acid, has been used as test solute. The retention factor (k) of this compound has been measured in MEEKC at several values of pH and the retention factor-pH profile has been established. As log P<sub>o/w</sub> correlates with log k<sub>MEEKC</sub> for neutral compounds, this correlation has been used to estimate the logarithm of the octanol-water partition coefficient of the neutral (log P<sub>o/w(HA)</sub>), and the fully ionized (log P <sub>o/w(A-)</sub>) forms of naproxen. Then, the logarithm of the octanol-water distribution coefficient (log D<sub>o/w</sub>) of the partially ionized form of the acid has been estimated. The comparison of the estimated values with the ones obtained experimentally using the classical procedures, such as the shake-flask method, shows differences under 0.4 log D<sub>o/w</sub> units either if the acid is partially ionized or in its neutral form in the most part of the pH range. However, the method overestimates the log D<sub>o/w </sub>of the highly (&gt;99.5 %) or fully ionized form of naproxen.
Highlights
Lipophilicity, which is defined as the ability of a compound to be dissolved in lipids or non-polar solvents, is a key factor in drug discovery
As expected, Equation 4 shows a good correlation between log Po/w and log kMEEKC for neutral compounds, and it is very similar to Equations 1 and 2
Accurate predictions of log Do/w have been obtained for naproxen at different degrees of ionization using the microemulsion electrokinetic chromatography (MEEKC) system presented in this work
Summary
Lipophilicity, which is defined as the ability of a compound to be dissolved in lipids or non-polar solvents, is a key factor in drug discovery. This property, among others, is related to the capacity of a substance to pass through different biological membranes, which are formed mainly by a lipid bilayer. The direct evaluation of this parameter (following the shake-flask method) is time-consuming and it is not fully automated. Because of these drawbacks, the development of faster high-throughput methods is of a great interest
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
