LIPOPHILICITY ASSESSMENT OF SPIRONOLACTONE BY MEANS OF REVERSED PHASE LIQUID CHROMATOGRAPHY AND BY NEWLY DEVELOPED...

Area of Science:

• Pharmacology
• Computational Chemistry
• Analytical Chemistry

Background:

• Spironolactone is a widely used diuretic and antihypertensive agent.
• Lipophilicity is a key parameter influencing drug absorption, distribution, metabolism, and excretion (ADME).
• Accurate determination of lipophilicity is crucial for drug development.

Purpose of the Study:

• To experimentally determine the lipophilicity of spironolactone using chromatographic methods.
• To calculate spironolactone's lipophilicity using various computational programs.
• To introduce and validate a novel method for calculating lipophilicity based on topological indices.

Main Methods:

• Experimental determination using reversed-phase thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC).
• Computational calculation using established software packages (AlogPs, logPKOWWIN, xlogP2, xlogP3, AClogP, AlogP, MlogP).
• Novel calculation of partition coefficients (logP1, logP2, logP3) using topological indices (e.g., 0B, 1B, W, 0χv, IB).

Main Results:

• Chromatographic parameters (Rm, logkw) were predicted using different stationary phases and mobile phases.
• Multiple computational methods provided various logP values for spironolactone.
• The novel method based on topological indices demonstrated good agreement with experimentally determined lipophilicity parameters (chromatography and shake flask method).

Conclusions:

• Topological indices provide a reliable and alternative method for calculating spironolactone's lipophilicity.
• The validated method can be used as an alternative to experimental determination and other computational approaches.
• This study highlights the utility of topological indices in predicting drug lipophilicity.