qNMR法测定片剂苯磺酸氨氯地平的含量

Content determination of amlodipine besylate tablet by quantitative nuclear magnetic resonance spectroscopy

本文利用定量核磁共振波谱法(qNMR)建立了测定片剂苯磺酸氨氯地平含量的分析方法。片剂样品经研磨称量后,加入氘代甲醇为溶剂、1,3,5-三甲氧基苯作为内标物进行混合。混合物经涡旋、超声和离心后取上清液转移入核磁管,对样品采集核磁共振氢谱(1H-NMR)。氢谱中以苯磺酸氨氯地平位于δ5.41的谱峰为检测定量峰,1,3,5-三甲氧基苯位于δ 6.07的谱峰为内标定量峰建立绝对定量方法。1H-NMR实验参数为:90度单脉冲序列,脉冲延迟时间30 s,扫描次数32次,采样温度308 K。实验结果显示苯磺酸氨氯地平与内标物的摩尔比在0.42~8.38的范围内具有良好的线性关系(R2=0.9973),精密度和稳定性试验的相对标准偏差(RSD)分别为0.45%(n=7)和0.44%。对于片剂样品,整个方法(包括目标组份的提取和定量核磁检测)重复性试验RSD为1.69%(n=6);三个不同浓度的加标回收率分别为103.86%、101.20%和99.69%。应用本方法对8个市售品牌的苯磺酸氨氯地平片剂进行了含量测定,结果显示建立的qNMR方法准确度高,重复性好,简便快捷,为片剂药品绝对含量的测定提供了新方法。

To established a quantitative nuclear magnetic resonance spectroscopy(qNMR)method for the content determination of amlodipine besylate tablets.The tablet sample was grounded and weighted before mixing with methal-d4 as solvent,1,3,5-trimethoxybenzene as internal standard.The mixture was votexed and centrifuged to achive good separation.The upper layer solution was quantitatively analyzed by 1H-NMR.The peaks ofδ5.41from amlodipine besylate andδ6.07 from 1,3,5-trimethoxybenzene were selected as quantitative peak and reference peak,respectively.Parameters used in 1H-NMR are:90 degree single pulse sequence,delay time 30 s,number of scans 32 and probe temperature 308 K.A good linear relationship was established for amlodipine besylate and 1,3,5-trimethoxybenzene between molar ratio range of 0.42-8.38 with correlative coefficient of 0.9973.Repeatability and Intermediate precision evaluation showed a relative standard deviation(RSD)of 0.45%(n=7)and 0.44%respectively.The robustness of this method was validated with a RSD of 1.69%(n=6).The spiked recoveries for amlodipine besylate tablet sample were 103.86%,101.20%and 99.69%for 3 sets of experiments.The established qNMR method was applied to analyze amlodipine besylate tablets from 8 different brands and the results showed this method is reliable and convenient with high precision and good repeatability,which could be apply as a general method for the content determination of medical tablets.