HEteronuclear Referencing for METRologic Isotope Calibration (HERMETRIC)

This work presents the concept of heteronuclear referencing for metrologic isotope calibration (HERMETRIC) as an innovative approach to quantitative NMR (qNMR) spectroscopy. The aim is to establish a metrologically based fundamental understanding that goes beyond traditional homonuclear NMR methods. In comparison to established quantitative methods-such as weighing, titration, chromatography, and complexometry-it is demonstrated that qNMR, as a primary method, can determine absolute amounts of substance directly without external calibration. At the same time, heteronuclear quantification opens new perspectives by enabling the direct traceability of all active nuclei to a universal qNMR primary standard. The concepts are intended to encourage the further establishment of qNMR as a powerful instrument in analytical chemistry and its incorporation into pharmacopoeias and other official standard protocols.