Isotopic 13C NMR spectrometry to assess counterfeiting of active pharmaceutical ingredients: Site-specific 13C content of aspirin and paracetamol

Abstract

Isotope profiling is a well-established technique to obtain information about the chemical history of a given compound. However, the current methodology using IRMS can only determine the global 13C content, leading to the loss of much valuable data. The development of quantitative isotopic 13C NMR spectrometry at natural abundance enables the measurement of the 13C content of each carbon within a molecule, thus giving simultaneous access to a number of isotopic parameters. When it is applied to active pharmaceutical ingredients, each manufactured batch can be characterized better than by IRMS. Here, quantitative isotopic 13C NMR is shown to be a very promising and effective tool for assessing the counterfeiting of medicines, as exemplified by an analysis of aspirin (acetylsalicylic acid) and paracetamol (acetaminophen) samples collected from pharmacies in different countries. It is proposed as an essential complement to 2H NMR and IRMS.