Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
College of Pharmacy, Xinjiang Medical University, Urumqi 830017, China.
Int J Mol Sci. 2024 Sep 27;25(19):10442. doi: 10.3390/ijms251910442.
As a salt-type compound, mosapride citrate's metabolism and side effects are correlated with its salt-forming ratio. Several techniques were developed in this work to compare various quantitative nuclear magnetic resonance (qNMR) methodologies and to quantitatively examine the content of raw materials. Among the qNMR techniques, methods for H NMR and F NMR were developed. Appropriate solvents were chosen, and temperature, number of scans, acquisition time, and relaxation delay parameter settings were optimized. Maleic acid was chosen as the internal standard in H NMR, and the respective characteristic signals of mosapride and citrate were selected as quantitative peaks. The internal standard in F NMR analysis was 4,4'-difluoro diphenylmethanone, and the distinctive signal peak at -116.15 ppm was utilized to quantify mosapride citrate. The precision, repeatability, linearity, stability, accuracy, and robustness of the qNMR methods were all validated according to the ICH guidelines. By contrasting the outcomes with those from high-performance liquid chromatography (HPLC), the accuracy of qNMR was assessed. As a result, we created a quicker and easier qNMR approach to measure the amount of mosapride citrate and evaluated several qNMR techniques to establish a foundation for choosing quantitative peaks for the qNMR method. Concurrently, it is anticipated that various selections of distinct quantitative objects will yield the mosapride citrate salt-forming ratio.
作为一种盐型化合物，枸橼酸莫沙必利的代谢和副作用与其成盐比例有关。本工作开发了几种技术，比较了各种定量核磁共振（qNMR）方法，并定量检查了原料的含量。在 qNMR 技术中，开发了 H NMR 和 F NMR 方法。选择了适当的溶剂，并优化了温度、扫描次数、采集时间和弛豫延迟参数设置。在 H NMR 中选择马来酸作为内标，选择莫沙必利和柠檬酸盐各自的特征信号作为定量峰。F NMR 分析中的内标为 4,4'-二氟二苯甲酮，利用 -116.15 ppm 处的特征信号峰来定量枸橼酸莫沙必利。根据 ICH 指南验证了 qNMR 方法的精密度、重复性、线性、稳定性、准确性和稳健性。通过将结果与高效液相色谱（HPLC）的结果进行对比，评估了 qNMR 的准确性。因此，我们创建了一种更快、更简单的 qNMR 方法来测量枸橼酸莫沙必利的含量，并评估了几种 qNMR 技术，为 qNMR 方法选择定量峰奠定了基础。同时，预计不同的定量对象选择将产生枸橼酸莫沙必利的成盐比例。
