2022 journal article

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

JOURNAL OF MASS SPECTROMETRY, 57(6).

co-author countries: United States of America πŸ‡ΊπŸ‡Έ
author keywords: high-throughput screening; IR-MALDESI; normalization; Orbitrap mass spectrometer
MeSH headings : Drug Discovery; High-Throughput Screening Assays; Lasers; Spectrometry, Mass, Electrospray Ionization / methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
Source: Web Of Science
Added: June 20, 2022

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.