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On the utility of nonuniformly sampled two‐dimensional NMR spectra in the pharmaceutical industry
Author(s) -
Szigetvári Áron,
Szántay Csaba
Publication year - 2021
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.5085
Subject(s) - chemistry , heteronuclear molecule , two dimensional nuclear magnetic resonance spectroscopy , sampling (signal processing) , decoupling (probability) , analytical chemistry (journal) , spectrometer , spectral line , nuclear magnetic resonance spectroscopy , nuclear overhauser effect , free induction decay , nuclear magnetic resonance , spin echo , chromatography , physics , stereochemistry , optics , magnetic resonance imaging , medicine , control engineering , astronomy , detector , radiology , engineering
In this work, we discuss representative examples of the application of nonuniform sampling (NUS) in small‐molecule structure determination in a pharmaceutical research and development and quality control setting. We demonstrate the advantages of NUS over traditional sampling in various industrial applications of nuclear magnetic resonance (NMR). We propose an optimal trade‐off between the quality and the time efficiency of ‘routine’ measurements, as demonstrated via a test sample of vinpocetine analyzed on a ‘work horse’ NMR spectrometer. In addition, we present case studies where the application of NUS contributed significantly to the successful completion of some challenging structure determination task at hand. To that end, in some cases, we combined NUS with a method of decoupling in the indirect dimension that gives ‘constant time’ nuclear Overhauser effect spectroscopy (NOESY) and ‘constant time’ heteronuclear multiple bond correlation (HMBC) spectra. NUS proved to be superior over traditional sampling even for the analysis of trace impurities, where the need to cope with a thousand‐fold or even larger dynamic range and low signal‐to‐noise ratio for the impurity signals is quite a challenge.