A simplified high-pressure liquid chromatography method for determining lipophilicity for structure-activity...

Area of Science:

• Analytical Chemistry
• Pharmacology
• Chromatography

Background:

• Quantitative structure-activity relationships (QSAR) are crucial for drug discovery.
• Chromatographic parameters offer valuable descriptors for QSAR modeling.
• Octadecyl-bonded silica columns provide a robust platform for lipophilicity assessment.

Purpose of the Study:

• To correlate chromatographic parameters (log kappa", log VR, and retention index I) with biological activity for sulfonamides and barbiturates.
• To compare the predictive power of log kappa" versus log VR in QSAR models.
• To present methods for controlling column activity and selecting mobile phases.

Main Methods:

• Utilized a deactivated octadecyl-bonded silica column with a water-methanol mobile phase at physiological pH and ionic strength.
• Correlated log kappa" (a measure of lipophilicity) with biological activities like protein binding, minimum inhibitory concentration, hypnotic activity, cell division inhibition, and brain respiration inhibition.
• Employed statistical analysis, including F-tests, to compare the goodness-of-fit for regressions using log kappa" and log VR.

Main Results:

• For sulfonamides, log kappa" and log VR showed statistically similar performance in predicting biological endpoints.
• For barbiturates, log kappa" and retention index (I) also demonstrated comparable predictive power across various biological activities.
• The study found no significant difference in the biological correlation capabilities between log kappa" and log VR or I.

Conclusions:

• Both log kappa" and log VR are effective chromatographic descriptors for QSAR studies of sulfonamides and barbiturates.
• The choice between log kappa" and log VR may not critically impact the biological activity prediction accuracy.
• The study provides practical guidance on column activity control and mobile phase selection for methanol-aqueous systems.