Mass spectrometry analysis of new chemical entities for pharmaceutical discovery

Abstract

In this Section, we review the applications of mass spectrometry for the analysis and purification of new chemical entities (NCEs) for pharmaceutical discovery. Since the speed of synthesis of NCEs has dramatically increased over the last few years, new high throughput analytical techniques have been developed to keep pace with the synthetic developments. In this Section, we review both novel, as well as modifications of commonly used mass spectrometry techniques that have helped increase the speed of the analytical process. Part of the review is devoted to the purification of NCEs, which has undergone significant development in recent years, and the close integral association between characterization and purification to drive high throughput operations. At the end of the Section, we review potential future directions based on promising and exciting new developments.

Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search

“…Herein, we report on the use of flow-injection (FI) data-dependent MS/MS combined with automated library search for the identification of pharmacologically active compounds in tablets and tablet residues. FI is the simplest form of rapid sample introduction into the mass spectrometer, and is widely used for the analysis of new chemical entities for pharmaceutical discovery [35]. A major drawback to FI-MS is ion suppression due to coeluting sample components.…”

Design and Synthesis of Conformationally Constrained Cyclophilin Inhibitors Showing a Cyclosporin‐A Phenotype in C. elegans

“…This provides a means of driving improvements to ligand design. [21] The role played by mass spectrometry (MS) in drug development has increased in significance over the last ten years, whether as a screen for large ligand libraries [22] or to probe ligand-substrate interactions. [23] With regard to the latter, specific applications have been developed for determining stoichiometry and dissociation constants for biological complexes.…”

Liquid Chromatography-Mass Spectrometric Multiple Reaction Monitoring-based Strategies for Expanding Targeted Profiling towards Quantitative Metabolomics

“…The hybrid liquid chromatography-mass spectrometry technology (LC-MS) using an atmospheric pressure ionization source (API) as the interface has proven to be the cornerstone analytical tool for most bioactive small-molecule assays [11][12][13][14][15][16], due to its inherently high compatibility with various drug-like chemicals with basic physiochemical properties [17,18], i.e., the capability of efficient separation and sensitive detection of a wide diversity of molecular species without the need for derivatization. Furthermore, the MS-based methodology has increasingly occupied a more prominent position than nuclear magnetic resonance in broad-range metabolic profiling and comprehensive metabolomics studies [6,[19][20][21].…”