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Dittakavi, Sreekanth; Mahadevan, Lavanya; Chandrashekar, Devaraj Venkatapura; Bhamidipati, Ravi Kanth; Joghee, Suresh; Dhakshinamoorthy, Saravanakumar; Li, Ziyu; Baerenz, Felix; Tennagels, Norbert; Mullangi, Ramesh

doi:10.1002/bmc.4846

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“…For ESI, different technologies such as the RapidFire system in BLAZE-mode (Bretschneider et al, 2019) or ADE-OPI MS approach have been described for enzymatic-type assays (H€ abe et al, 2020;Simon et al, 2021a). The versatility of the instrument setup allows the analysis of many different biomolecules including lipids (Highkin et al, 2011;Dittakavi et al, 2020), peptides (Hutchinson et al, 2011;Liddle et al, 2020), and metabolites (Soulard et al, 2008;Maxine et al, 2009), from a wide range of matrix systems including blood, plasma (Highkin et al, 2011;Bretschneider et al, 2017) and cell lysates (Gordon et al, 2016;Dittakavi et al, 2020). Ambient ionization, such as desorption electrospray ionization (DESI), which commonly does not require sample preparation, is a new and attractive alternative for HT analysis.…”

Section: Blaze Modementioning

confidence: 99%

Advances in high‐throughput mass spectrometry in drug discovery

et al. 2022

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High‐throughput (HT) screening drug discovery, during which thousands or millions of compounds are screened, remains the key methodology for identifying active chemical matter in early drug discovery pipelines. Recent technological developments in mass spectrometry (MS) and automation have revolutionized the application of MS for use in HT screens. These methods allow the targeting of unlabelled biomolecules in HT assays, thereby expanding the breadth of targets for which HT assays can be developed compared to traditional approaches. Moreover, these label‐free MS assays are often cheaper, faster, and more physiologically relevant than competing assay technologies. In this review, we will describe current MS techniques used in drug discovery and explain their advantages and disadvantages. We will highlight the power of mass spectrometry in label‐free in vitro assays, and its application for setting up multiplexed cellular phenotypic assays, providing an exciting new tool for screening compounds in cell lines, and even primary cells. Finally, we will give an outlook on how technological advances will increase the future use and the capabilities of mass spectrometry in drug discovery.

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