定量核磁共振氢谱测定新药替格瑞洛

doi:10.11938/cjmr20192705

摘要/Abstract

摘要： 本文建立了基于核磁共振氢谱（¹H NMR）测定新药替格瑞洛绝对含量的方法.采用Bruker Avance 300型NMR谱仪，以磺胺多辛为内标；以替格瑞洛中质子信号δ_H 7.14（2H，m）和δ_H 7.04（1H，s），磺胺多辛质子信号δ_H 8.04（1H，s）、δ_H 7.73（2H，d）和δ_H 6.54（2H，d）作为定量峰；以氘代甲醇（CD₃OD）为溶剂进行测定.测定条件为：探头温度为308 K，谱宽为3 511.5 Hz，中心频率为1 470.6 Hz，脉冲翻转角为θ=30°，延迟时间为10 s，采样次数为16，线宽因子为0.3 Hz.在此实验条件下，替格瑞洛样品与内标磺胺多辛的定量峰分离良好，实验结果精密度较高、重复性较好、线性范围较宽，其线性拟合方程为：Y=1.053X-0.081（r=0.996，n=5）.最终测得样品中替格瑞洛含量为99.4%，相对标准偏差（RSD）为0.20%.该方法简便、准确、快速，适用于替格瑞洛样品的绝对含量测定.

关键词: 核磁共振氢谱, 替格瑞洛, 含量测定

Abstract: A novel proton nuclear magnetic resonance (¹H NMR) method for determining the absolute content of ticagrelor was proposed. The ideal spectra were obtained on a Bruker Avance-300 spectrometer with deuterated methanol (CD₃OD) as the solvent and sulfadoxin as the internal standard. The ticagrelor signals at δ_H 7.14 (2H, m) and δ_H 7.04 (1H, s), as well as those of sulfadoxin at δ_H 8.04 (1H, s), δ_H 7.73 (2H, d) and δ_H 6.54 (2H, d), were selected for quantitative analysis. The detection conditions were as following:probe temperature 308 K, spectrum width 3 511.5 Hz, center frequency 1 470.6 Hz, pulse angle θ=30°, delay time (d1) 10 s, number of scans 16 and line broadening 0.3 Hz. The signals from ticagrelor and internal standard sulfadoxin showed good separation, precision, reproducibility, and wide linearity ranges with Y=1.053X-0.081 (r=0.996, n=5). The content of ticagrelor was estimated to be 99.4% (RSD=0.20%). This method was proven simple, accurate and rapid.

Key words: proton nuclear magnetic resonance (¹H NMR), ticagrelor, content determination

中图分类号:

张芬芬, 沈文斌, 徐开兵, 杨明. 定量核磁共振氢谱测定新药替格瑞洛[J]. 波谱学杂志, 2020, 37(2): 216-223.

ZHANG Fen-fen, SHEN Wen-bin, XU Kai-bing, YANG Ming. A Proton Nuclear Magnetic Resonance Method for Quantitative Analysis of Ticagrelor[J]. Chinese Journal of Magnetic Resonance, 2020, 37(2): 216-223.

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