The new face of isotopic NMR at natural abundance

Abstract

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 H, C, N, O or S. However, in the 1980s, the direct access to Site-specific Natural Isotope Fractionation by Nuclear Magnetic Resonance (SNIF-NMR ) 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- 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- C NMR approach delivers direct access to position-specific C isotope content at natural abundance. After highlighting the application scope of irm-NMR ( H and C), this article describes the major improvements which made possible to reach the required accuracy of 1‰ (0.1%) in irm- 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). Copyright © 2016 John Wiley & Sons, Ltd.

Position‐specific 13C/12C analysis of amino acid carboxyl groups – automated flow‐injection analysis based on reaction with ninhydrin

“…17 Methods for PSIA of small molecules based on Stable Isotope Natural Fractionation-Nuclear Magnetic Resonance (SNIF-NMR or 2 H NMR) have also been developed although these techniques are typically applied to compounds that can be prepared in large amounts and high purity, for example ethanol distilled from European wines. 19 These techniques now provide the basis for the authentication of a number of natural products, and reference materials (RMs) exist for the PSIA of ethanol with certified 2 H/ 1 H ratios of both methyl and methylene groups (e.g. European Commission, Joint Research Centre BCR-656 and BCR-660).…”

Position‐specific 15N isotope analysis in organic molecules: A high‐precision 15N NMR method to determine the intramolecular 15N isotope composition and fractionation at natural abundance

“…Peak areas of 15 N peaks were determined by the curve-fitting process implemented within Perch (Perch NMR Software, University of Kuopio, Finland). For the one-pulse isotopic 13 C NMR, the methodology was already described, [9] and details are given in SI.…”

“…Isotope ratio measured by 13 C NMR (irm-13 C NMR) has been successfully tested and proved as an efficient tool for the 13 C positionspecific determination. [9] However, the determination of the intramolecular isotopic profile by the one-pulse approach is a lengthy experiment due to the low natural abundance of 13 C (1.1%), its relatively small gyromagnetic ratio, and a long longitudinal relaxation. As a result, it requires relatively large amount of material and/or long analysis duration.…”

Isotopomics by isotope ratio monitoring by 13C nuclear magnetic resonance spectrometry on cutting agents in heroin: A new approach for illicit drugs trafficking route elucidation

“…The measurement of position-specific 2 H isotope compositions based on nuclear magnetic resonance spectrometry (SNIF-NMR™) was first proposed by Martin et al 12 Nowadays, irm-2 H NMR is a well-established technique for food authentication and is used for the official control of wine, spirits, fruit juices, and flavors. 13,14 However irm-2 H NMR still suffers from a number of limitations, notably the 2 H low sensitivity, the potential H-exchange during the manufacturing process, the lack of resolution due to overlapping signals and the low molecular dynamic ranges because of the quadrupolar relaxation, limiting irm-2 H NMR to molecules of low molecular weight (< 250 g/mol).…”

“…[15][16][17] The main difficulty of irm-13 C NMR is obtaining a high level of precision: a standard deviation lower than 1‰ due to the low isotopic 13 C deviation range (δ 60‰). Despite this, the method has been applied successfully in several fields 14 including isotope profiling of active pharmaceutical ingredients such as paracetamol 18 and natural products such as caffeine. 19 Another limitation of irm-13 C NMR is the experiment duration which might be prohibitive for routine analysis.…”