The new face of isotopic NMR at natural abundance.

The most widely used method for isotope analysis at natural abundance is isotope ratio monitoring by Mass Spectrometry (irm-MS) which provides bulk isotopic composition in 2 H, 13 C, 15 N, 18 O or 34 S. However, in the 1980s, the direct access to Site-specific Natural Isotope Fractionation by Nuclear Magnetic Resonance (SNIF-NMRTM ) was immediately recognized as a powerful technique to authenticate the origin of natural or synthetic products. The initial - and still most popular - application consisted in detecting the chaptalization of wines by irm-2 H NMR. The approach has been extended to a wide range of methodologies over the last decade, paving the way to a wide range of applications, not only in the field of authentication but also to study metabolism. In particular, the emerging irm-13 C NMR approach delivers direct access to position-specific 13 C isotope content at natural abundance. After highlighting the application scope of irm-NMR (2 H and 13 C), this article describes the major improvements which made possible to reach the required accuracy of 1‰ (0.1%) in irm-13 C NMR. The last part of the manuscript summarizes the different steps to perform isotope analysis as a function of the sample properties (concentration, peak overlap) and the kind of targeted isotopic information (authentication, affiliation).