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

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. Graphical abstract