Acoustic Ejection/Full-Scan Mass Spectrometry Analysis for High-Throughput Compound Quality Control

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Drug Discovery

Background:

• High-throughput compound quality control (QC) is crucial in drug discovery for assay-ready plates, compound integrity, and reaction monitoring.
• Traditional liquid chromatography-mass spectrometry (LC-MS) workflows face significant throughput limitations due to the large number of samples involved.
• Existing chromatography-free mass spectrometry (MS) approaches have yielded mixed results for rapid analysis.

Purpose of the Study:

• To demonstrate the feasibility of acoustic ejection-mass spectrometry (AE-MS) for high-throughput compound QC in miniaturized formats.
• To evaluate AE-MS for both qualitative and quantitative analyses, aiming for reduced sample consumption and increased analytical speed.

Main Methods:

• Utilized acoustic ejection-mass spectrometry (AE-MS) in full-scan mode for direct, contactless liquid sampling.
• Compared AE-MS performance against conventional LC-MS for qualitative QC and relative quantification.
• Developed a data processing platform using commercial tools to manage AE-MS generated data.

Main Results:

• AE-MS achieved a 1000-fold reduction in sample consumption and a 30-fold reduction in analysis time compared to LC-MS.
• AE-MS provided comparable results to LC-MS for identifying the presence/absence of compounds in qualitative QC.
• AE-MS demonstrated utility in the relative quantification of compounds in serial dilutions and reaction substrates.

Conclusions:

• Acoustic Ejection-Mass Spectrometry (AE-MS) is a viable and efficient technique for high-throughput compound QC.
• AE-MS significantly overcomes the analytical bottleneck in compound QC workflows, offering substantial improvements in speed and sample economy.
• The developed data processing platform facilitates straightforward data handling, eliminating the need for custom software.