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Use of quantitative 1H and 13C NMR to determine the purity of organic compound reference materials: a case study of standards for nitrofuran metabolites

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Abstract

Comparability of measurement results and their metrological traceability to the International System of Units (SI) are fundamental tools to ensure reliable decisions in the social sphere, commerce, and science. The use of appropriate references in analytical chemistry, such as certified reference materials (CRMs) of high purity substances, is one of the required procedures to obtain traceable measurements. When commercial standards with non-certified purity values are used, traceability must be achieved by determining the purity of the standard using a potential primary reference measurement procedure or other appropriate methods. Quantitative nuclear magnetic resonance (qNMR) is a technique with the potential to be used in primary measurement procedures. This work presents the determination of purity by 1H qNMR for nitrofuran metabolites 3-amino-2-oxazolidinone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), and 1-aminohydantoin (AHD). Furthermore, a recent qNMR method developed by our group to improve the quantitative performance of measurements using 13C nucleus was used to determine the purity of semicarbazide (SEM) nitrofuran metabolite. Purity values obtained by qNMR for AOZ, AMOZ, and AHD standards were compared to values obtained by the mass balance approach using a suite of analytical methods: Karl Fischer (KF) coulometric titration and thermogravimetry (TG) for the determination of water and residual solvents, gas and liquid chromatography for the determination of impurities structurally related to the metabolites. The results obtained by qNMR and mass balance were consistent.

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Data availability

Data generated or analyzed during this study, such as, NMR spectra; TG and DSC plots; GC-FID and HPLC-DAD chromatograms; and tables containing replicates and per aliquot results, are included in this published article and its ESM file. The datasets provided in the ESM are available in a single file in PDF format.

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Acknowledgments

We would like to acknowledge the Carlos Chagas Filho Research Support Foundation of the Rio de Janeiro State (FAPERJ) which financially supported this work; the National Council for Scientific and Technological Development (CNPq) for the research grant to Prof. Francisco R. de Aquino Neto; the CNRMN/CCS/UFRJ for the NMR spectrometer used in 13C NMR analysis; the LARA/IF/UFF for the semicarbazide isotope ratio analysis; and Dr. Eveline Robertis (Laboratory of Thermal Analysis and Particular Materials, Inmetro) for the TG experiments.

Funding

This work was financially supported by the Carlos Chagas Filho Research Support Foundation of the Rio de Janeiro State - FAPERJ (grant number E-26/110.135/2013). Prof. Francisco R. de Aquino Neto awarded a research grant from the National Council for Scientific and Technological Development (CNPq) and FAPERJ (grant numbers 303086/2015-7 and E-26/202.834/2017, respectively).

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Authors and Affiliations

  1. National Institute of Metrology, Quality and Technology (Inmetro), Scientific Metrology and Technology Directorate (Dimci), Chemical and Thermal Metrology Division (Dimqt), Av. Nossa Senhora das Graças, 50, Xerém, Duque de Caxias, RJ, 25250-020, Brazil

    Fernando G. M. Violante, Wagner Wollinger, Evelyn F. Guimarães & Bruno C. Garrido

  2. Chemistry Institute (IQ), Laboratory for the Support of Technological Development (Ladetec), Federal University of Rio de Janeiro (UFRJ), Avenida Horácio Macedo, 1281, Polo de Química, bloco C, Cidade Universitária, Rio de Janeiro, RJ, 21941-598, Brazil

    Francisco Radler de Aquino Neto

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  1. Fernando G. M. Violante
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  2. Wagner Wollinger
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  3. Evelyn F. Guimarães
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Contributions

Bruno C. Garrido and Wagner Wollinger developed and performed the NMR experiments. Fernando G. M. Violante and Evelyn F. Guimarães developed and performed the experiments based on chromatographic techniques, as well as the KF analyses. Prof. Francisco R. Aquino Neto coordinated the study and evaluated the results. All authors reviewed and approved the manuscript.

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Correspondence to Fernando G. M. Violante.

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Violante, F.G.M., Wollinger, W., Guimarães, E.F. et al. Use of quantitative 1H and 13C NMR to determine the purity of organic compound reference materials: a case study of standards for nitrofuran metabolites. Anal Bioanal Chem 413, 1701–1714 (2021). https://doi.org/10.1007/s00216-020-03134-1

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