Integrating automation and LC/MS for drug discovery bioanalysis

Area of Science:

• Pharmacology and Toxicology
• Analytical Chemistry
• Laboratory Automation

Background:

• Traditional bioanalytical sample handling is time-consuming and can be a bottleneck in drug discovery.
• High-throughput analysis requires efficient and reliable sample preparation methods.

Purpose of the Study:

• To develop and validate a novel, integrated, and automated approach for sample handling in drug discovery bioanalysis.
• To enhance the efficiency and throughput of biological sample preparation and analysis.

Main Methods:

• Developed a semi-automated 96-well liquid-liquid extraction technique for biological fluids.
• Integrated sample collection, processing, and high-throughput liquid chromatography-mass spectrometry (LC/MS) with multiple reaction monitoring (MRM).
• Evaluated liquid-handling workstations, dilution schemes, and biological fluid choices.

Main Results:

• Reduced sample preparation time from 4 hours to 1.5 hours per 96-well plate.
• Achieved equivalent drug quantitation results compared to conventional methods.
• Doubled the efficiency of drug discovery bioanalysis assays per month.

Conclusions:

• The integrated automated sample handling approach significantly increases bioanalysis efficiency in drug discovery.
• This method is compatible with high-throughput LC/MS and LC/TOF/MS, enabling accurate drug quantitation and disposition characterization.
• The developed process offers a scalable solution for future automated sample preparation workstations.