^1H NMR法定量测定奥沙西泮杂质Ⅰ对照品的含量  

Determination of impurity Ⅰ reference substance of oxazepam by ^1H NMR

作　　者：周晓力[1] 马迅[1] 陈华[1] 南楠[1] 

机构地区：[1]中国食品药品检定研究院,北京100050

出　　处：《药物分析杂志》2016年第9期1696-1699,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的：建立采用^1H NMR法测定奥沙西泮杂质Ⅰ的绝对含量。方法：以对苯二甲酸二甲酯基准试剂为内标,以氘代氯仿为溶剂,采用Bruker AvanceⅢ500型核磁共振谱仪,noesyigld1d脉冲序列在恒温25℃下获取^1H NMR谱,测定奥沙西泮杂质Ⅰ的含量,驰豫延迟时间为25 s。结果：以奥沙西泮杂质Ⅰ的峰（δ5.97）及对苯二甲酸二甲酯（δ8.10）峰作为定量峰,将样品与内标的NMR峰面积比对其质量比绘制标准曲线,奥沙西泮杂质Ⅰ的线性范围为8～24 mg,相关系数为0.999 9,精密度RSD为0.08%（n=5）,重复性RSD为0.43%（n=6）,定量限为0.338 mg;核磁共振法测得奥沙西泮杂质Ⅰ的含量为99.8%,与质量平衡法测得结果 99.6%基本一致。结论：采用核磁共振定量的方法可测定奥沙西泮杂质Ⅰ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 develop a proton-nuclear magnetic resonance（^1H NMR） approach for the determination of impurity Ⅰ of oxazepam.Methods：^1H NMR spectra were obtained in chloroform-d by using an Avance Ⅲ 500 spectrometer with noesyigld1 d pulse sequence at 25 ℃,the internal standard was dimethyl terephthalate（DMT）,and the relaxation delay time was 25 s.Results：The peak at δ 5.97 of impurity Ⅰ of oxazepam and δ 8.10 of DMT were used for quantitation.The linear relationship between peak area ratio and weight ratio of sample（δ 5.97） to inner standard DMT（δ 8.10） was obtained ranged from 8 mg to 24 mg,with correlative coefficient of 0.999 9.The precision RSD was 0.08%（n=5）,and the repeatability RSD was 0.43%（n=6）.The LOQ was 0.338 mg.The result determined by the method（99.8%） was consistent with the result by mass balance method（99.6%）.Conclusion：The established quantitative nuclear magnetic resonance（QNMR） method can be used for the quantitative determination of impurity Ⅰ of oxazepam,which is effective and reliable as a good complementarity for the determination of the reference standards.

关 键 词：去甲羟基安定 奥沙西泮杂质Ⅰ 杂质对照品 绝对含量测定 对苯二甲酸二甲酯 1H核磁共振定量(1H QNMR) 方法验证 

分 类 号：R917[医药卫生—药物分析学]