Application of Benchtop NMR for API Quantification in Modern Drug Product Development and Supply

Benchtop NMR systems have garnered significant attention in Pharmaceutical Sciences due to their capability to deliver rapid quantitative analysis (qNMR) of active pharmaceutical ingredients (APIs), in addition to providing structural elucidation and enabling real-time chemical reaction monitoring. This study employed qNMR to quantify the API content in granulation process intermediates, necessitating large sample sizes of ≥5g to ensure representative content determination and to avoid sample fractioning. In comparison to HPLC analysis, qNMR demonstrated clear advantages by eliminating labor-intensive sample preparation, such as the secondary and tertiary dilutions required to achieve the linear calibration range of an on-line UV detector. The inclusion of an internal standard facilitated correction for volume displacement and matrix effects, enhancing the accuracy of the measurements. The qNMR method outlined in this study proved to be equivalent to an orthogonal HPLC-based method. Furthermore, advancements in GMP-compliant software for Benchtop NMR systems have rendered them a viable option for future quality control (QC) methodologies.