Revision of USP Chapter <761> NMR Spectroscopy and <1761> Applications of NMR Spectroscopy

In the Pharmacopeial Forum, PF 48(4), revisions of USP chapters <761> Nuclear Magnetic Resonance Spectroscopy and <1761> Applications of Nuclear Magnetic Resonance Spectroscopy are being proposed. Comments can be submitted until September 30, 2022.

According to the 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."

<761> Nuclear Magnetic Resonance Spectroscopy

The proposal for the revised Chapter <761> is structured as follows:

• Introduction
• Qualification of NMR instruments
  - User Requirements Specification (URS)
  - Design Qualification (DQ)
  - Installation Qualification (IQ)
  - Operational Qualification (OQ)
  - Performance Qualification (PQ)
  - System Suitability Test (SST)
  - Qualification Test Procedures
• Qualitative and quantitative NMR analysis
  - Qualitative Applications
  - Quantitative Applications
• Validation and verification of NMR analytical procedures
  - Analytical Procedure Validation with Life Cycle Approach
  - Analytical Procedure Validation with Traditional Approach
  - Analytical Procedure Verification
• References

Compared to the currently valid version of the chapter (official as of May 1, 2018), the following changes, among others, were made:

• The life cycle approach to analytical procedure validation is introduced.
• The elements of qualification of NMR instruments are expanded. URS, DQ, and SST are included.
• The chapter on qualitative and quantitative NMR analysis was revised.
• An updated terminology framework was added.

<1761> Applications of Nuclear Magnetic Resonance Spectroscopy

First of all, it is proposed to change the title of the chapter to align with the other suite of spectroscopy chapters. The new title, "Nuclear Magnetic Resonance Spectroscopy—Theory and practice", also reflects the revised content within the chapter.

The revised Chapter <1761> is structured as follows:

• Introduction
  - Scope and Applicability
  - Audience
• Principles of NMR
• NMR Definitions 
  - Resonance, Signal, Spectrum, Pattern, Peak, Line, and Transition
• Characteristics of the NMR spectrum
  - Chemical Shift 
  - Coupling 
  - Spectral Intensity
• NMR Spectrometers
  - Magnet
  - Probe 
  - Console and Computer
• Instrument preparation
  - Magnet Shimming, Probe Tuning, and Matching
• Acquisition parameters
  - Spectral Width, Dwell Time, Number of Data Points, Acquisition Time, Number of Scans, Radio Frequency, Receiver Gain, and Pulse Width
• Other experimental considerations
  - Solvent Selection
  - Sample Preparation
• Post-acquisition data processing
  - Increasing the S/N Ratio or Spectral Resolution
  - Zero-Filling 
  - Fourier Transformation 
  - Phasing 
  - Baseline Correction 
  - Peak Picking 
  - Integration 
  - Advanced Processing
• Solution-state NMR applications
  - Structural Elucidation and Characterization
  - Identification 
  - Quantitation
• Two-dimensional NMR
• Benchtop NMR
  - Benchtop Time-Domain NMR Spectrometers
  - Benchtop Frequency-Domain NMR Spectrometers
  - Benchtop NMR Applications

The chapter has been thoroughly revised and reorganized. In comparison with the currently valid version (official as of May 1, 2013), the following new aspects, among others, are notable:

• Several subchapters, for example, "NMR Spectrometers" and "Post-acquisition Data Processing" were expanded.
• A new passage entitled "Characteristics of the NMR Spectrum" and two new sections, "Acquisition Parameters" and "Other Experimental Considerations" were added.
• A new subchapter on Benchtop NMR was added, including a discussion of both time- and frequency-domain techniques.
• The section on solid-state NMR spectroscopy was removed because a new general information chapter on the subject is being proposed.

Further information and a more detailed summary of the proposed revisions can be found in the two drafts published on PF Online.