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Position-Specific 13C Isotope Analysis by NMR as a Tool for Characterizing the Manufacturing Process Used and for Fighting Pharmaceutics Counterfeiting

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Handbook of Isotopologue Biogeochemistry

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Abstract

Counterfeits based on deliberate copying of processes for generic medicines are not straightforward to detect. Multidimensional isotope profiling is a useful tool for the characterization of the provenance of the active molecule. More parameters than the global isotope composition can be retrieved from isotope ratio measured by nuclear magnetic resonance spectrometry (irm-NMR). This has been demonstrated by the applications of irm-2H NMR on some active pharmaceutical ingredients (APIs) but it remains limited to rather small molecules (<300 g mol−1). Isotopic 13C NMR spectrometry measures the 13C content of each carbon position of the API, providing a unique 13C profile that reflects the whole history of the API including the raw materials and the manufacturing process used. Recent technological NMR developments have made further improvements to enhance sensitivity that allow the study of larger molecules and/or of low amount of material. The representation of the isotope profile can be considered as analogous to that carried out in “omic” approaches: comparison of data built up from a multiplicity of variables and collected from several samples using the same protocol, introducing then the notion of “isotopomics.” Isotopomics appears as a unique tool for tagganting each batch produced at natural isotopic abundance and can be used for traceability within the supply chain both by the manufacturer and by the regulatory bodies as a new parameter for the validation master file beside the mandatory impurities profile.

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Authors and Affiliations

  1. MIMM Team, CEISAM, UMR Nantes Université-CNRS, Nantes, France

    Gerald S. Remaud & Serge Akoka

  2. Eurofins Analytics France, Nantes, France

    Freddy Thomas

Authors
  1. Gerald S. Remaud
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  2. Serge Akoka
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  3. Freddy Thomas
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Correspondence to Gerald S. Remaud .

Editor information

Editors and Affiliations

  1. Dept Chem Sci & Eng, Tokyo Inst Tech, Yokohama, Kanagawa, Japan

    Naohiro Yoshida

  2. Earth-Life Sci Inst, Tokyo Inst Tech, Meguro-ku, Tokyo, Japan

    Alexis Gilbert

  3. Earth-Life Sci Inst, Tokyo Inst Tech, Meguro-ku, Tokyo, Japan

    Julien Foriel

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Remaud, G.S., Akoka, S., Thomas, F. (2023). Position-Specific 13C Isotope Analysis by NMR as a Tool for Characterizing the Manufacturing Process Used and for Fighting Pharmaceutics Counterfeiting. In: Yoshida, N., Gilbert, A., Foriel, J. (eds) Handbook of Isotopologue Biogeochemistry. Springer, Singapore. https://doi.org/10.1007/978-981-10-7048-8_41-1

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  • DOI: https://doi.org/10.1007/978-981-10-7048-8_41-1

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