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Related Concept Videos

Mass Spectrometry: Complex Analysis01:21

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Related Experiment Video

Updated: Sep 13, 2025

An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
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Single-Sample, Multiomic Mass Spectrometry for Investigating Drug Effects and Mechanisms.

Iqbal Mahmud1, Wai-Kin Chan1, Karen Yannell2

  • 1Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.

Journal of Proteome Research
|July 29, 2025
PubMed
Summary
This summary is machine-generated.

This study developed a multiomic method to analyze drug toxicity, revealing that l-Asparaginase (ASNase) impacts antioxidation and inflammation pathways. This approach can generate new hypotheses for reducing drug side effects.

Keywords:
Bio LC-MSasparaginaseautomated fractionationlipidomicsmetabolomicsmultiomicsproteomicstoxicity

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Drug attrition during development is often caused by poor therapeutic indexes.
  • Identifying mechanisms of drug toxicity is crucial for drug development.
  • l-Asparaginase (ASNase), used for pediatric acute lymphoblastic leukemia, has toxicity limitations in adults.

Purpose of the Study:

  • To develop and validate a multiomic method for elucidating drug toxicity mechanisms.
  • To profile the response to l-Asparaginase (ASNase) in immune-compromised mice.
  • To generate hypotheses for reducing ASNase toxicity while preserving efficacy.

Main Methods:

  • Performed longitudinal profiling of subtoxic and toxic doses of ASNase in mice.
  • Collected 20-μL whole blood samples, processed to plasma, and extracted metabolites, lipids, and proteins.
  • Utilized a triple quadrupole LC-MS/MS platform for targeted metabolomics, lipidomics, and proteomics analysis of 500+ metabolites, 750+ lipids, and 375 peptides.

Main Results:

  • Identified dose-dependent modulation of metabolites, lipids, and peptides.
  • Observed convergence of modulated molecules on antioxidation, inflammation, autophagy, and cell death pathways.
  • Demonstrated the ability of the multiomic workflow to generate new hypotheses regarding ASNase toxicity.

Conclusions:

  • The developed three-in-one LC-MS/MS workflow is effective for targeted multiomic analysis.
  • ASNase toxicity appears linked to antioxidation, inflammation, autophagy, and cell death pathways.
  • Inhibiting these pathways may offer a strategy to decrease ASNase toxicity and improve its therapeutic index.