NMR spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (¹H) to quantify chemicals is called quantitative ¹H-NMR (¹H qNMR). The quantitative method using ¹H qNMR for determining the purity or content of chemicals has been adopted into some compendial guidelines and official standards. However, there are still few reports in the literature regarding validation of ¹H qNMR methodology. Here, we coordinated an international collaborative study to validate a ¹H qNMR based on the use of an internal calibration methodology. Thirteen laboratories participated in this study, and the purities of three samples were individually measured using ¹H qNMR method. The three samples were all certified via conventional primary methods of measurement, such as butyl p-hydroxybenzoate Japanese Pharmacopeia (JP) reference standard certified by mass balance; benzoic acid certified reference material (CRM) certified by coulometric titration; fludioxonil CRM certified by a combination of freezing point depression method and ¹H qNMR. For each sample, ¹H qNMR experiments were optimized before quantitative analysis. The results showed that the measured values of each sample were equivalent to the corresponding reference labeled value. Furthermore, assessment of these ¹H qNMR data using the normalized error, E_n-value, concluded that statistically ¹H qNMR has the competence to obtain the same quantification performance and accuracy as the conventional primary methods of measurement.

由于信号强度与分子中每个原子核的数量成正比，因此NMR光谱法最近已用于确定具有计量溯源性的有机分子的绝对量。使用氢核（¹ H）定量化学物质的NMR方法称为定量¹ H-NMR（¹ H qNMR）。使用¹ H qNMR定量测定化学药品的纯度或含量的定量方法已被一些药典指南和官方标准所采用。然而，文献中关于¹ H qNMR方法论验证的报道仍然很少。在这里，我们协调了一项国际合作研究，以验证¹1 H NMR基于内部校准方法的使用。13个实验室参加了这项研究，并且使用¹ H qNMR方法分别测量了三个样品的纯度。这三个样品均通过常规的主要测量方法认证，例如通过质量平衡认证的对羟基苯甲酸丁酯日本药典（JP）参考标准；电量滴定法认证的苯甲酸认证参考物质（CRM）; 氟迪沙尼CRM通过冰点降低法和¹ H qNMR组合认证。对于每个样本，¹在定量分析之前，对1 H NMR实验进行了优化。结果表明，每个样品的测量值等于相应的参考标记值。此外，使用归一化误差E _n值评估这些¹ H qNMR数据得出的结论是，统计学上¹ H qNMR具有与常规主要测量方法相同的定量性能和准确度的能力。