Quantitative 1 H NMR methodology for purity assay with high accuracy

Nuclear magnetic resonance (NMR) has fast emerged as a quantitative platform for it offered numerous advantages over chromatographic methods in analyzing purity and determining content of organic compounds. However, the mechanism of parameter settings has not been further investigated causing the improper or incorrect use in the widespread qNMR applications. This study aims to construct a quantitative 1 H NMR methodology based on the experiment optimization and simulation and explain the impact of parameter settings on accuracy. We successfully applied the proposed 1 H qNMR method with the internal standard method to assess the purity of ofloxacin, a commonly used antibacterial drug. The study showed that parameter settings, including flip angle, relaxation delay, transmitter frequency offset, scan number and data point, had different effects on the quantification errors (0.5 % to 8.9 %). The method validation proved that the 1 H qNMR methodology delivered high accuracy with the measurement uncertainty (0.60 %). The results demonstrated that the proposed 1 H qNMR method provided clear guidance on the practical implementation of accurate quantification of low molecular mass compounds (< 500 g/mol).