Benchtop NMR spectroscopy for pharmacopeial assays of over-the-counter medicines

The increased adoption of benchtop nuclear magnetic resonance (NMR) technology into a variety of industries has been facilitated by the enhanced automatability, accessibility, and affordability offered by these permanent magnet-based systems. In recent years, there has been an active interest to incorporate this technology into both academia and industry to benefit research, undergraduate teaching laboratories, and introduce more widespread applicability in quality control (QC) assays. However, many standardization bodies in the pharmaceutical industry, including the United States Pharmacopeia (USP), make use of the most commonly used techniques in pharmaceutical QC for many of the assays included in their published standard, such as gas chromatography (GC), high-performance liquid chromatography (HPLC), and titration.

Recently, we published a white paper in collaboration with the USP, wherein we demonstrated the efficacy of benchtop NMR for QC assays by using over-the-counter (OTC) medicines as an example, and we supplemented our analyses with quantum mechanics-NMR-based software to greatly decrease the time and effort required to obtain and analyze quantitative NMR (qNMR) results. The results were compared to those obtained using HPLC following the exact methods published in the USP monographs. In Figure 1, the chemical structures of the active pharmaceutical ingredients (APIs) analyzed as part of this project are presented.

Figure 1. Chemical structures of APIs analyzed in the context of the white paper.

The OTC medicines assayed in this project include products containing ibuprofen, naproxen sodium, acetylsalicylic acid (regular), acetylsalicylic acid (delayed-release), and multi-component acetaminophen and caffeine. In all cases, the results obtained using a traditional manual integration approach match those from USP-ID, the quantum mechanics-NMR-based software offered by the USP, very closely. This approach demonstrates that the combination of benchtop NMR technology and quantum mechanics can significantly reduce the time requirements and lower accessibility barriers for industrial QC.

For a thorough description of the work performed as part of this study, including NMR spectra, a detailed overview of the USP-ID software, a full breakdown of the qNMR results, and an in-depth description of the methodologies used, please check out the full white paper here! If you have any questions about how benchtop NMR could be incorporated into your pharmaceutical QC workflows, please don’t hesitate to contact us.