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Isotope Ratio Monitoring by NMR: Part 3 – New Applications for Traceability of Active Pharmaceutical Ingredients

  • Gérald S. Remaud
  • Serge Akoka
Reference work entry

Abstract

Isotopic ratio measurement by nuclear magnetic resonance (irm-NMR) is recognized as a powerful technique for assessing the traceability of active pharmaceutical ingredients (APIs). The results obtained with this method are extremely valuable for the detection of a number of different types of counterfeiting: (i) the use of synthetic ingredients when a natural origin is labeled, (ii) a deliberately copied process, (iii) patent infringement of current patents for generic medicines, (iv) products that are not made in the specified country of origin, and (v) diversion. It has been further improved by the use of irm-13C NMR, which provides major advantages such as (i) an increase in the number of parameters allowing the determination of the molecular fingerprint and (ii) the possibility of analyzing molecules for which 2H-NMR is particularly difficult or even impossible. 13C also enables the use of multi-pulse sequences to increase the sensitivity such as INEPT. The results obtained show that this strategy can be used effectively to determine the 13C distribution within a given molecule and to compare accurately the differences in the isotopic distribution between different samples of the given molecule, in a very short analytical time, even though absolute values of specific isotopic deviations cannot be provided. The aim of this chapter is to describe the general principles of isotopic analysis by NMR and applications for API traceability. Perspectives are also presented, based on some of the most recent methodological developments.

Keywords

Irm-NMR Isotope ratio Isotopic abundance Isotopic composition Isotopic fractionation 2D NMR INEPT Traceability Active pharmaceutical ingredients (APIs) 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM UMR CNRS 6230)Université de NantesNantesFrance

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