Posting Date: 26–Feb–2021
Expert Committee: USP qNMR Expert Panel of the General Chapters—Chemical Analysis Expert Committee, with members from General Chapters—Physical Analysis and Excipients – Simple Excipients Expert Committees.
Input Deadline: 28–Mar–2021
Proposed New Title: <1XXX> Solid-state NMR Spectroscopy – Theory and Practice
Suggested audience: Suppliers and manufactures of drug substance, drug products, excipients, contract manufacturing organizations, drug testing organizations and drug products related regulatory agencies, QA/QC specialists.
Estimated proposal PF: Pharmacopeial Forum 47(5)
Background and objectives: USP general chapters 〈761〉 Nuclear Magnetic Resonance Spectroscopy and 〈1761〉 Applications of Nuclear Magnetic Resonance Spectroscopy are currently being revised by the quantitative nuclear magnetic resonance (qNMR) Expert Panel of the General Chapters—Chemical Analysis Expert Committee.
USP intends to develop a new informational general chapter <1xxx> on solid-state NMR spectroscopy which will provide useful information on current scientific and regulatory approaches for the analysis of pharmaceuticals.
Currently official general chapter <1761> contains informational content related to solid-state NMR spectroscopy, but the proposed revisions of the chapter would remove this content and propose the revised content in the new informational general chapter dedicated to solid-state NMR spectroscopy.
Description of scope and application: To provide theoretical and practical aspects for the application of solid-state NMR spectroscopy. Guidance for experimental setup and conducting solid-state NMR experiments will be presented. Applications to drug substance, drug product, and excipient characterization will also be included.
Preliminary outline: The following represents the sections for the proposed General Chapter
- INTRODUCTION – Elaboration on the differences between solution-state NMR and solid-state NMR spectroscopy. The utility of solid-state NMR spectroscopy and applications in ensuring pharmaceutical quality will be highlighted.
- SOLID-STATE NMR SPECTROSCOPY THEORY AND TECHNIQUES – Basic theory of solid-state NMR spectroscopy, one-dimensional and two-dimensional routine and advanced techniques are presented, including relaxation theory, cross-polarization magic angle spinning, high-power decoupling, and multi-dimensional correlation techniques.
- PROCEDURE – Information on setting up a solid-state NMR spectroscopy is proposed, including selecting and optimizing spectrometer parameters for a general method and for specific applications. Best practices and considerations for sample preparation and sample packing is presented. Development of a procedure, including selecting nuclei for analysis, rotor size, cross-polarization times, magic angle speed, and relaxation times is discussed. Post-acquisition data processing practices will also be proposed.
- APPLICATIONS – Examples of validated methods and pharmaceutical applications will be presented. The section will include applications like polymorphism, quantitation of forms, structure elucidation, crystallography, phase homogeneity, drug-drug and drug-excipient interactions, drug product and excipient characterization, and physical and chemical stability prediction. Chemical modalities and biologics will also be covered in this section.
- EMERGING TECHNIQUES – This section will present various emerging solid-state NMR spectroscopy techniques, including bench-top instrumentation, dynamic nuclear polarization, fast magic angle spinning, and multi-sample solid-state NMR.
Anticipated implementation timing: To be determined based on stakeholder feedback.
Additional Information:
- Stimuli to the revision process article, Quantitative Nuclear Magnetic Resonance (qNMR), a Metrological Method—Proposed Revisions to the USP General Chapters on NMR, Nuclear Magnetic Resonance Spectroscopy 〈761〉 and Applications of Nuclear Magnetic Resonance Spectroscopy 〈1761〉, PF 46(6) [November 1 2020 – January 31, 2021].
- USP-NF General Chapter, 〈761〉 Nuclear Magnetic Resonance Spectroscopy, Current DocID: GUID-B980A615-B451-42FF-AC40-4CB8B64163E3_3_en-US
- USP-NF General Chapter 〈1761〉 Applications of Nuclear Magnetic Resonance Spectroscopy, Current DocID: GUID-D84DE004-6D63-48D4-BC58-90A1830C5484_1_en-US
Contact: Lucy Botros, Scientific Liaison at lyb@usp.org
CN-21-042-00