Practical guide on MALDI-TOF MS method development for high throughput profiling of pharmaceutically relevant, small molecule chemical reactions

摘要

High-throughput experimentation (HTE) offers means to allow medicinal chemists to synthesize a variety of pharmaceutically active compounds in an ultra-high throughput fashion, which also requires the development of an ultra-fast analytical method in order to reduce the bottleneck of post-reaction data analysis. We recently demonstrated MALDI-TOF-MS as an ultra-fast screening tool for the profiling of nano-mole C-N coupling reactions in a 1536 well plate at the rate of 0.3-0.4 s per sample. This work will cover MALDI method development steps including determination and optimization of sample concentration, spotting and drying methods, matrix selection, and quantitation approaches for high throughput pharmaceutical reaction profiling. The purpose of this work is to serve as a practical guide for organic and medicinal chemists to quickly develop a high throughput MALDI-TOF-MS method for routine screening of multi-well plate based chemical reactions without any MALDI plate modification or product tagging. (C) 2020 Elsevier Ltd. All rights reserved.