USP general chapters Nuclear Magnetic Resonance Spectroscopy <761> and Applications of Nuclear Magnetic Resonance Spectroscopy <1761> are currently being revised by the quantitative nuclear magnetic resonance (qNMR) Expert Panel. Since the last revision in 2013, there has been a surge in the utilization of NMR as a quantitative tool to determine purity of organic compounds and the composition of mixtures, and there is an urgent need to provide current guidance on the use of qNMR for applications within scope of the USP. The main purpose of the revision is to standardize guidance for the adoption of qNMR as a measurement method that is consistent with the already established principles and guidance framework of metrology—the science of measurement and its application. In addition to enabling the application of science and quality risk management, the revisions are aligned with the new general chapter Analytical Procedure Life Cycle <1220> that defines validation as a process of design and development, qualification, and continued verification. The concepts of analytical target profile (ATP) and target measurement uncertainty (TMU) are introduced as the principal benchmarks to be used for validation of analytical procedures based on qNMR. A holistic understanding of the measurement procedure and system that accounts for uncertainty contributions from specified sources can be used to qualify the NMR instrument and qNMR method using certified reference materials (CRMs) and thus simplify the validation of the final compound-specific analytical procedure. For example, linearity, a traditional method performance characteristic, can be verified as part of the operational qualification (OQ) of the NMR instrument and may not have to be verified as part of the qualification of the specific qNMR analytical procedure.
