Benchtop nuclear magnetic resonance performance evaluation according to ASTM E691-22 on a population of instruments: Molar substitution determination in hydroxypropyl betadex as a case study for use in quality control environments.

Abstract

The inclusion of quantitative nuclear magnetic resonance (qNMR) spectroscopy in industry has historically been stifled by a lack of accessibility, caused in-part by the large costs of traditional high-field spectrometers, the maintenance required for these, and the expertise necessary to manage and use them. In recent years, the emergence of benchtop NMR technology, an accessible, affordable, and automatable alternative, has led to a more feasible incorporation of NMR into quality control spaces, an area traditionally reserved for other techniques such as gas chromatography and liquid chromatography, which are routinely combined with detection techniques such as mass spectrometry. While these techniques are commonly used in analyzer-type applications using gold standard methods of analysis, wherein an instrument is dedicated to performing specific assays, this remains uncommon for NMR. Herein, we perform a full method verification using benchtop qNMR on a population of benchtop NMR instruments according to the ASTM designation E691-22, a standard used to determine the precision of a test method. To our knowledge, this is the first published example of this type of study for benchtop NMR spectroscopy. For this work, a total of five analysts performed assays on 23 different benchtop NMR instruments for the analysis of hydroxypropyl betadex according to the USP-NF method, and the results are compared using a variety of statistical methods. The results of this work demonstrate that benchtop NMR technology is effective and robust under repeatability and reproducibility conditions and is a powerful tool for these types of routine quality control analyses.