USP-NF Stimuli Article on Consistent NMR Terminology

In the Pharmacopeial Forum, PF 48(4), a stimuli article entitled "Consistent Terminology for Advancement of NMR Spectroscopy" was published. The stimuli article is available on PF Online. The deadline for submitting comments is September 30, 2022.

Background

Nuclear Magnetic Resonance (NMR) Spectroscopy is an analytical procedure based on the magnetic properties of certain atomic nuclei placed in a magnetic field. NMR spectroscopy can be seen as a powerful tool for structure elucidation and identification. It can also be used for quantitative measurements (qNMR).

NMR spectra contain a wealth of information. However, the spectra can become very complex, even for chemically simple molecules. The interpretation and evaluation of complex NMR spectra require a basic theoretical understanding of the method, but also a broad experience and the ability to analytical thinking. 

Revision of USP Chapters <761> and <1761>

Proposals to revise USP chapters <761> Nuclear Magnetic Resonance Spectroscopy and <1761> Applications of Nuclear Magnetic Resonance Spectroscopy also appear in PF 48(4).

According to the corresponding briefing notes, the revision of the two chapters has three main purposes:

• "1) to update the content with modern technologies and contemporary practices of NMR spectroscopy;
• 2) to expand coverage of quantitative NMR (qNMR) applications to better reflect the established utility and growing use of qNMR in pharmaceutical analysis and metrology and
• 3) explain essential concepts that underlie advanced methodologies for both qualitative and quantitative NMR analysis."

A summary of the proposed revisions is available by following this link.

Content of the Stimuli Article

The authors of the stimuli article write that "the history, evolution, and (in-)consistency of widely applied quantitative NMR (qNMR) terminology calls for re-examination and more precise alignment with fundamental principles, especially considering its directly applicable quantum mechanical foundation." With this article, they want to build "the foundation for a modular, coherent, and standardized terminology, a condition necessary for a healthy life cycle of research data, including their management and reuse."

The article starts with an introduction, which highlights the complexity of NMR spectra and the difficulties associated with their precise interpretation and characterization. In the literature, the term multiplets (m) is often used when publishing NMR spectra. According to the authors, "this is unfortunate, as all the underlying coupling and chemical information is disregarded whenever the multiplet designation is used. [...] The abundance of multiplets as a blanket term in publications, with the meaning of 'unknown splitting pattern,' mirrors the likewise haphazard handling of other NMR terms that are used and accepted widely yet may not possess a strictly agreed-upon meaning."

Based on this observation, the article attempts to provide the theoretical and experimental rationale for a clear terminology in NMR spectroscopy. In particular, the following terms are explained and defined:

• Resonance
• Signal
• Spectrum
• Pattern
• Peak
• Line
• Transition
• Splitting
• Multiplicity
• Multiplet
• Resolution
• Dispersion