Importance of Purity Evaluation and the Potential of Quantitative ¹H NMR as a Purity Assay

In any biomedical and chemical context, a truthful description of chemical constitution requires coverage of both structure and purity. This qualification affects all drug molecules, regardless of development stage (early discovery to approved drug) and source (natural product or synthetic). Purity assessment is particularly critical in discovery programs and whenever chemistry is linked with biological and/or therapeutic outcome. Compared with chromatography and elemental analysis, quantitative NMR (qNMR) uses nearly universal detection and provides a versatile and orthogonal means of purity evaluation. Absolute qNMR with flexible calibration captures analytes that frequently escape detection (water, sorbents). Widely accepted structural NMR workflows require minimal or no adjustments to become practical 1H qNMR (qHNMR) procedures with simultaneous qualitative and (absolute) quantitative capability. This study reviews underlying concepts, provides a framework for standard qHNMR purity assays, and shows how adequate accuracy and precision are achieved for the intended use of the material.在所有生物医学与化学研究场景中，对化学组成的准确描述需同时涵盖结构与纯度信息。这一要求适用于所有药物分子，无论其处于研发阶段（从早期发现到获批药物）还是来源（天然产物或合成产物）。纯度评估在药物发现项目中，以及当化学物质与生物学和/或治疗效果相关联时尤为关键。相较于色谱法与元素分析法，定量核磁共振（quantitative NMR, qNMR）采用近乎通用的检测方式，为纯度评估提供了通用且正交的技术手段。采用灵活校准方式的绝对定量核磁共振技术，可检测到通常难以被检出的分析物（如水、吸附剂）。被广泛采用的结构核磁共振工作流程，仅需少量调整甚至无需改动，即可成为兼具定性与（绝对）定量能力的实用型1H定量核磁共振（1H qNMR，又称qHNMR）分析流程。本研究梳理了其核心概念，为标准qHNMR纯度测定建立了一套完整框架，并阐明了如何针对材料的预期用途实现足够的准确度与精密度。