Normalization techniques for high-throughput screening by infrared matrix-assisted laser desorption electrospray ionization mass spectrometry.


Journal

Journal of mass spectrometry : JMS
ISSN: 1096-9888
Titre abrégé: J Mass Spectrom
Pays: England
ID NLM: 9504818

Informations de publication

Date de publication:
Jun 2022
Historique:
revised: 21 05 2022
received: 02 05 2022
accepted: 26 05 2022
pubmed: 10 6 2022
medline: 11 6 2022
entrez: 9 6 2022
Statut: ppublish

Résumé

Mass spectrometry (MS) is an effective analytical tool for high-throughput screening (HTS) in the drug discovery field. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MS is a high-throughput platform that has achieved analysis times of sub-seconds-per-sample. Due to the high-throughput analysis speed, methods are needed to increase the analyte signal while decreasing the variability in IR-MALDESI-MS analyses to improve data quality and reduce false-positive hits. The Z-factor is used as a statistic of assay quality that can be improved by reducing the variation of target ion abundances or increasing signal. Herein we report optimal solvent compositions for increasing measured analyte abundances with direct analysis by IR-MALDESI-MS. We also evaluate normalization strategies, such as adding a normalization standard that is similar or dissimilar in structure to the model target drug, to reduce the variability of measured analyte abundances with direct analyses by IR-MALDESI-MS in both positive and negative ionization modes.

Identifiants

pubmed: 35678360
doi: 10.1002/jms.4869
pmc: PMC9287052
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e4869

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM087964
Pays : United States
Organisme : AbbVie
ID : None
Organisme : NIH HHS
ID : R01GM087964
Pays : United States

Informations de copyright

© 2022 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.

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Auteurs

Kevan T Knizner (KT)

FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.

Michael C Bagley (MC)

FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.

Fan Pu (F)

Drug Discovery Science and Technology, AbbVie Inc., North Chicago, Illinois, USA.

Nathaniel L Elsen (NL)

Drug Discovery Science and Technology, AbbVie Inc., North Chicago, Illinois, USA.

Jon D Williams (JD)

Drug Discovery Science and Technology, AbbVie Inc., North Chicago, Illinois, USA.

David C Muddiman (DC)

FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.
Molecular Education, Technology and Research Innovation Center (METRIC), North Carolina State University, Raleigh, North Carolina, USA.

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