High-throughput logP measurement using parallel liquid chromatography/ultraviolet/mass spectrometry and...

Area of Science:

• Analytical Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Accurate lipophilicity (logP) measurement is crucial in drug discovery.
• Traditional logP methods can be time-consuming and labor-intensive.
• High-throughput screening demands efficient and robust analytical techniques.

Purpose of the Study:

• To develop a novel, high-throughput method for logP determination.
• To leverage liquid chromatography/ultraviolet/mass spectrometry (LC/UV/MS) for logP analysis.
• To establish a correlation between logP and logk (capacity factor) for rapid screening.

Main Methods:

• Utilized liquid chromatography/ultraviolet/mass spectrometry (LC/UV/MS) for compound analysis.
• Determined logP by correlating with logk values derived from retention times.
• Employed MS-friendly mobile phases (ammonium carbonate or formate with methanol) for accuracy and robustness.
• Integrated extracted ion chromatograms (EICs) to avoid impurity interferences and allow compound pooling.

Main Results:

• Successfully established a correlation between logP and logk using a defined set of standards.
• Demonstrated the method's applicability on both single and parallel LC/UV/MS systems.
• Achieved a high-throughput capability of analyzing over 1000 compounds per day.
• Validated the approach for screening lead compounds and their analogs in drug discovery.

Conclusions:

• The proposed LC/UV/MS approach offers a novel and efficient solution for high-throughput logP measurement.
• This method enhances accuracy by minimizing interferences and allows for pooled injections.
• The system is robust and suitable for routine screening in pharmaceutical research and development.