Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

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Abstract

Continuous improvements in mass spectrometry (MS) have resulted in the widespread availability and adoption of high‐resolution mass spectrometry (HRMS) across laboratories worldwide. The capabilities and the associated advantages of HRMS make it an invaluable analytical tool for analyte characterization, screening, and quantification methodologies for a wide scope of applications across pharmaceutical development. These applications include drug discovery, product characterizations of both small molecules and novel drug modalities, in vitro and in vivo metabolism studies, post‐approval quality control, and pharmacovigilance. This review gives an overview of the current capabilities of HRMS and its pharmaceutical applications in 2020, and provides a perspective on the future of HRMS within the pharmaceutical industry.

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Most cited references 79

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A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

David E Gordon, Gwendolyn M Jang, Mehdi Bouhaddou … (2020)

SUMMARY The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

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The Lancet Commission on pollution and health

Philip J. Landrigan, Richard C. Fuller, Nereus J R Acosta … (2018)

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Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome

C Wong, C W K Lam, A K L Wu … (2004)

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.

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Author and article information

Contributors

Stephen W. Holman:

ORCID: https://orcid.org/0000-0003-4370-1088

stephen.holman@astrazeneca.com

Journal

Journal ID (nlm-ta): Anal Sci Adv

Journal ID (iso-abbrev): Anal Sci Adv

Journal ID (doi): 10.1002/(ISSN)2628-5452

Journal ID (publisher-id): ANSA

Title: Analytical Science Advances

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2628-5452

Publication date (Electronic): 29 January 2021

Publication date Collection: April 2021

Volume: 2

Issue: 3-4 , Annual Reviews 2020 – Recent Advances in Analytical Sciences ( doiID: 10.1002/ansa.v2.3-4 )

Pages: 142-156

Affiliations

[ ¹ ] Chemical Development Pharmaceutical Technology & Development Operations, AstraZeneca Macclesfield UK

Author notes

[*] [* ] Correspondence

Stephen W. Holman, Chemical Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UK.

Email: stephen.holman@ 123456astrazeneca.com

Author information

Stephen W. Holman https://orcid.org/0000-0003-4370-1088

Article

Publisher ID: ANSA202000149

DOI: 10.1002/ansa.202000149

PMC ID: 10989654

PubMed ID: 38716455

SO-VID: 9b56877c-6069-41f3-a456-a07e093c0196

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 18 December 2020

Date received : 13 November 2020

Date accepted : 21 December 2020

Page count

Figures: 5, Tables: 1, Pages: 15, Words: 9771

Custom metadata

source-schema-version-number 2.0

cover-date April 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:26.03.2024

Keywords: high‐resolution,hrms,mass spectrometry,ms,pharmaceutical,pharma

Data availability:

Keywords: high‐resolution, hrms, mass spectrometry, ms, pharmaceutical, pharma

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Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

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HR-EBSD (High Resolution - Electron Back Scatter Diffraction)

Most cited references 79

A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

The Lancet Commission on pollution and health

Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome

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