Full Spectrum Isotopic ¹³C NMR Using Polarization Transfer for Position-Specific Isotope Analysis

For the last ten years, quantitative isotope ratio monitoring ¹³C NMR (irm-¹³C NMR) has been successfully tested and proven as an efficient tool for the determination of position-specific ¹³C/¹²C ratios. Several applications in different domains have shown the interest in this technique. In the context of origin assignment, the possibility to track the distribution network of illicit drugs or cutting agents is of prime importance. However irm-¹³C NMR still suffers from a relative lack of sensitivity limiting its dissemination among control laboratories. Improvements were proposed to reduce experiment time by using the INEPT sequence ("Insensitive Nuclei Enhanced by Polarization Transfer") based on polarization transfer from highly sensitive ¹H to less sensitive ¹³C. Several applications based on the use of the one bond scalar coupling between ¹H and ¹³C (¹ J_CH) have shown the potential of this methodology in terms of short experimental duration. However, the isotopic information given by quaternary carbons was lost. The aim of this study is to extend this approach by using short- and long-range coupling (¹ J_CH, ² J_CH, and ³ J_CH) in order to have access to all ¹³C/¹²C position-specific ratios, i.e., acquisition of the full spectrum (FS-INEPT). It is shown that this innovative tool provides both sensitivity gain-thanks to the long-range polarization transfer-and appropriate repeatability. The relative isotopic profiles allowed the classification of two cutting agents, caffeine and paracetamol (acetaminophen), according to their origin, as it was previously observed with "classical" irm-¹³C NMR but consuming much less sample and/or reducing the experimental time.