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

  • 摘要: 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(1 H-NMR)。氢谱中以苯磺酸氨氯地平位于 δ 5.41 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。1 H-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。

     

    Abstract: 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 1 H-NMR. The peaks of δ 5.41from amlodipine besylate and δ 6.07 from 1,3,5-trimethoxybenzene were selected as quantitative peak and reference peak,respectively. Parameters used in 1 H-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.

     

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