定量核磁共振法测定4种磷酸二酯酶-5抑制剂的含量

Quantitative determination of four phosphodiesterase 5 inhibitors by proton nuclear magnetic resonance

目的:建立定量核磁共振法(qNMR)测定那莫西地那非、豪莫西地那非、硫代艾地那非和伪伐地那非4种磷酸二酯酶-5(PDE-5)抑制剂的含量。方法:采用Bruker Ascend 500 MHz核磁共振仪采集一维定量氢谱,90°脉冲,延迟时间为20 s,采样次数为64次,测定温度25℃,以对苯二甲酸二甲酯为内标,氘代氯仿(CDCl3)为溶剂,对4种PDE-5抑制剂进行定量研究。结果:样品与内标物定量峰分离良好,4种成分在各自线性范围内线性关系良好(R2>0.999 2),进样精密度和重复性好。那莫西地那非、豪莫西地那非、硫代艾地那非和伪伐地那非的含量(n=6)分别99.2%(RSD=0.27%)、99.4%(RSD=0.28%)、99.1%(RSD=0.18%)和99.3%(RSD=0.24%),与质量平衡法测定结果比较,两者基本一致。结论:本文建立的q NMR法测定4种PDE-5抑制剂的含量准确可靠,简便快速,为该类成分的含量测定和对照品的标定提供了新的测定方法。

Objective:To establish a quantitative nuclear magnetic resonance(q NMR)method for the determination of norneosildenafil,homosildenafil,thioaildenafil,and pseudovardenafil.Methods:Proton nuclear magnetic resonance spectroscopy(1HNMR)spectra were obtained in CDCl3 with the internal standard of dimethyl terephthalate using a Bruker Ascend 500 spectrometer,the parameters were setup as follows:the pulse sequence was 90o,the relaxation delay time was 20 s,the number for scanning was 64,and the experiment temperature was controled at 25℃.Results:The linearity of four components were linear in the concentration ranges(R2>0.999 2),and the precision,stability,and repeatability were good.The contents(n=6)of norneosildenafil,homosildenafil,thioaildenafil,and pseudovardenafil by q NMR were 99.2%(RSD=0.27%),99.4%(RSD=0.28%),99.1%(RSD=0.18%),and 99.3%(RSD=0.24%),respectively,which were almost consistent with those by mass balance method.Conclusion:The q NMR method is accurate,reliable,simple,and rapid for the quantitative determination of the above four phosphodiesterase 5(PDE-5)inhibitors.The study provides a new way for the content determination and calibration of reference materials.