Utilizing Ultra-High Throughput Mass Spectrometry Tools to Expedite Sample Analysis in Drug Discovery

Description:
High-throughput experimentation (HTE) workflows enable medicinal chemists to conduct multiple parallel reactions to synthesize a large array of diverse pharmaceutical substances at micromole/nanomole scales. To overcome analytical challenges arising from slower data acquisition/analysis times of Ultra-High Performance Liquid Chromatography (UHPLC), Ultra-High Throughput Mass Spectrometry (u-HTMS) capabilities were evaluated. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) and Acoustic Ejection Mass Spectrometry (Echo-MS) were implemented due to their advantageous sampling rates of <1 sec per sample. A systematic MALDI-MS study was carried out across various drug modalities ( small molecules, peptides and antibodies) to assess the impact of different parameters such as matrix and sample preparation procedures. The results of this study enabled the development of effective high throughout MALDI-MS analysis methods for various analytes by providing guidance on signal optimization. Moreover, the utility of Echo-MS for screening small molecule chemical reaction plates was evaluated using both the Quadrupole-Time of Flight (Q-TOF) and the Triple Quadrupole (QQQ) MS platforms. The results obtained from Echo-MS were then compared to traditional state-of-the-art UHPLC methods using UV-Vis or Corona-charged Aerosol Detection (CAD) detection techniques. The outcome of this study demonstrated the superiority of u-HTMS capabilities as rapid analytical screening tools that can accelerate the drug design cycle.

Speaker: Debopreeti Mukherjee - Merck & Co., Inc.