A robust, viable, and resource sparing HPLC-based logP method applied to common drugs

Area of Science:

• Pharmacology
• Analytical Chemistry
• Medicinal Chemistry

Background:

• Experimentally determined drug lipophilicity (logP) values are scarce in scientific literature.
• Existing logP data often relies on in silico predictions, which may lack accuracy.
• Accurate lipophilicity is crucial for understanding drug behavior and optimizing pharmacokinetic (PK) models.

Purpose of the Study:

• To develop a robust, resource-efficient method for measuring drug partition coefficient (logP) using reverse-phase high-performance liquid chromatography (RP-HPLC).
• To provide reliable, experimentally determined logP values for common drugs.
• To establish a high-throughput method for estimating drug lipophilicity.

Main Methods:

• Developed and validated a RP-HPLC method for logP determination.
• Utilized calibration curves generated from reference standards with known logP values.
• Measured logP for twelve common drugs at pH 6 and pH 9.

Main Results:

• The RP-HPLC method successfully measured logP for twelve common drugs.
• Obtained logP values showed general agreement with existing HPLC-based literature data.
• Results partially correlated with logP values from other methodologies, with deviations up to ±10%.

Conclusions:

• The developed RP-HPLC method provides a facile and reliable alternative for estimating drug logP without octanol or computational approaches.
• This method facilitates high-throughput logP estimation, crucial for drug discovery and development.
• Generating a larger dataset of reliable logP values can significantly enhance medicinal chemistry and PK models.