What Is the Accuracy of Quantitative Analysis by Low-Field NMR Spectroscopy Using Internal Standard: Systematic Study of Finished Medicinal Products?

Abstract Quantitative nuclear magnetic resonance (qNMR) is considered as a powerful tool for measuring the absolute amount of small molecules in complex mixtures. In this study, the performance of quantitative analysis on low-field NMR (LF NMR) devices was evaluated for a representative set of 33 finished medicinal products. Sample preparation, critical acquisition, and processing parameters were systematically evaluated. Recovery rates varied between 97 and 103% were achieved by signal-to-noise ratio (SNR) equal to 300 using deuterated solvents. For non-deuterated solvents, the recovery rates between 95 and 105% were observed at this SNR value. Average bias values in comparison with the reference high-field NMR were found to be 1.4% and 2.6% for deuterated and non-deuterated solvents, respectively. Erroneous results can be obtained for non-deuterated solvents when the integrated signals are situated close to solvent suppression regions. Validation results in terms of precision and reproducibility demonstrate that the LF qNMR method is fit-for-purpose for the marketed pharmaceutical products.