^19F qNMR在含氟制剂含量测定中的应用

Application of ^(19)F qNMR in the assay of fluorine-containing preparation

目的:建立^(19)F核磁共振定量(qNMR)测定片剂中含氟药物含量的方法。方法:以4,4′-二氟二苯甲酮为内标,氘代DMSO为溶剂,采用反门控去耦的zgfhigqn.2脉冲序列,利用^(19)F qNMR测定卡格列净片中卡格列净含量。试验参数如下:谱宽SW=40×10-6,射频中心频率O1P=-110×10-6,采样点数TD=128 k,采样时间AQ=3.5 s,弛豫延迟时间D1=20 s,扫描次数32次。结果:通过简单的过滤或离心处理后,使用^(19)F qNMR测得6片卡格列净片中卡格列净含量分别为98.2%、98.9%、101.0%、99.7%、99.2%,与HPLC外标法测定结果相近。结论:^(19)F qNMR可以用于含氟药物制剂中药品含量测定,这种技术前处理简单,检测速度快,不受辅料等干扰,可以用于含氟药物制剂含量的高通量测定。

Objective：To establish a 19F quantitative nuclear magnetic resonance（q NMR） method to determine the content of active pharmaceutical ingredient（API） in fluorine-containing preparation. Methods：In 19F qNMR experiments,4,4 ′-difluorobenzophenone was used as an internal standard. DMSO-d6 was used as solvent and zgfhigqn-.2 pulse sequence w6 ith inverse gated decoupling was applied. Other parameters were as follows：SW=40×10^46,O1 P=-110×10-6,TD=128 k,AQ=3.5 s,D1=20 s and NS=32. Results：After simple pre-treatment of filtration or centrifuge,the content of canagliflozin in 5 tablets were measured using ^（19）-qNMR. The results were 98.2%,98.9%,101.0%,99.7% and 99.2%,respectively. The results were similar to those from HPLC method. Conclusion：19F qNMR can be used in determining the contents of fluorine-containing APIs in tablets. This method only requires minimal pre-treatment and its testing speed is rapid. Meanwhile,the excipients have no interference with the determination. This technology is suitable for high-throughput measuring the API content in fluorine-containing preparation.