High-resolution acoustic ejection mass spectrometry for high-throughput library screening.

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Drug Discovery

Background:

• Drug candidate libraries require efficient quality assessment for effective drug discovery.
• Traditional methods are often time-consuming, limiting throughput.
• High-resolution mass spectrometry offers potential for rapid analysis.

Purpose of the Study:

• To develop and validate a high-throughput quality assessment method for drug candidate libraries using acoustic ejection mass spectrometry (AEMS).
• To introduce a novel high-throughput quantification method (HTQuant) for library components.
• To demonstrate the general applicability of the AEMS approach for diverse compound libraries.

Main Methods:

• Utilized high-resolution acoustic ejection mass spectrometry (AEMS) for sample introduction from 1536-well plates.
• Employed 2.5 nL sample droplets and pneumatically assisted electrospray ionization at a rate of one sample per second.
• Developed specialized software for data interpretation and a high-throughput quantification (HTQuant) method.

Main Results:

• Achieved 180-fold higher throughput compared to the industry standard LC/PDA/ELSD/MS method with similar compound coverage.
• Demonstrated high reproducibility in peak areas (4.4% CV) for quantification.
• Showcased the method's applicability to both focused and diverse compound libraries.

Conclusions:

• AEMS provides a rapid and efficient approach for high-throughput quality assessment of drug candidate libraries.
• The HTQuant method enables accurate quantification without internal standards, streamlining workflows.
• This technology supports AI-driven drug discovery by providing large volumes of high-quality data.