¹H_NMR定量测D₃-吗啡对照品的含量

目的: 采用 ¹H NMR法建立了D₃-吗啡绝对含量的测定方法。方法: 以对苯二甲酸二甲酯基准试剂为内标,以氘代甲醇为溶剂,采用Bruker Avance Ⅲ 500型核磁共振谱仪,zg30脉冲序列在恒温25 ℃下获取¹H NMR谱,测定D₃-吗啡的含量,驰豫延迟时间为20 s。结果: 以D₃-吗啡的峰(δ 5.62)及对苯二甲酸甲酯(δ8.12)峰作为定量峰,测得精密度RSD为0.09%(n=5),重复性RSD为0.69%(n=6)。将样品与内标的NMR峰面积比对其质量比绘制标准曲线,相关系数为0.999 9,氘代吗啡的线性范围为5~17 mg;定量限为0.872 mg。核磁共振法测得样品的含量为93.9%,与质量平衡法结果93.3%及HPLC外标法结果94.1%一致。结论: 采用核磁共振定量的方法可测定D₃-吗啡的绝对含量,此方法准确快捷,简单易行,是对标准物质绝对含量测定的一种良好的补充方法。

Objective: To establish a proton-nuclear magnetic resonance(¹H NMR) approach for the determination of D₃-morphine. Methods: ¹H NMR spectra were obtained in methanol-d₄ by using an Avance Ⅲ 500 spectrometer with zg30 pulse sequence at a constant temperature 25 ℃, the internal standard of dimethyl terephthalate(DMT), the relaxation delay time of 20 s. Results: The peaks at δ 5.62 of D₃-morphine and δ 8.12 of DMT were used for quantitation.The precision RSD was 0.09%(n=5) and the repeatability RSD was 0.69%(n=6).The linear relationship between peak area ratio and weight ratio of sample D₃-morphine(δ 5.62) to inner standard DMT(δ 8.12) was obtained as the D₃-morphine ranged from 5 mg to 17 mg, with correlative coefficient of 0.999 9.The LOQ was 0.872 mg.The content determined by the method(93.9%) was consistent with the result by mass balance method(93.3%) and HPLC external standard method(94.1%). Conclusion: The QNMR method can be used for the quantitative determination of D₃-morphine.It is indicated that QNMR is effective and reliable as a good complementarity for the determination of the reference standards.

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