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Updated: Jun 6, 2026

Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
NMR spectroscopy as a tool to close the gap on metabolite characterization under MIST
Janet Caceres-Cortes1, Michael D Reily
1Bioanalytical and Discovery Analytical Sciences, Pharmaceutical Clinical Optimization Department, Bristol-Myers Squibb, Princeton, NJ, 08543, USA. janet.cacerescortes@bms.com
Abstract:
Withdrawals from the market due to unforeseen adverse events have triggered changes in the way therapeutics are discovered and developed. This has resulted in an emphasis on truly understanding the efficacy and toxicity profile of new chemical entities (NCE) and the contributions of their metabolites to on-target pharmacology and off-target receptor-mediated toxicology. Members of the pharmaceutical industry, scientific community and regulatory agencies have held dialogues with respect to metabolites in safety testing (MIST); and both the US FDA and International Conference on Harmonisation have issued guidances with respect to when and how to characterize metabolites for human safety testing. This review provides a brief overview of NMR spectroscopy as applied to the structure elucidation and quantification of drug metabolites within the drug discovery and development process. It covers advances in this technique, including cryogenic cooling of detection circuitry for enhanced sensitivity, hyphenated LC-NMR techniques, improved dynamic range through new solvent-suppression pulse sequences and quantitation. These applications add to the already diverse NMR toolkit and further anchor NMR as a technique that is directly applicable to meeting the requirements of MIST guidelines.
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