qNMR-HPLC联用快速测定西洛他唑杂质Ⅰ校正因子  

Rapid Determination of Cilostazol Impurity Ⅰ Correction Factor by qNMR-HPLC

作　　者：濮恒婷 刘静[1] 许卉[2] 刘阳[1] 张庆生[1] PU Hengting;LIU Jing;XU Hui;LIU Yang;ZHANG Qingsheng(National Institutes for Food and Drug Control,Beijing 102629,China;School of Pharmaceutical Sciences,Yantai University,Yantai 264005,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]烟台大学药学院,山东烟台264005

出　　处：《中国药学杂志》2024年第16期1540-1544,共5页Chinese Pharmaceutical Journal

基　　金：中国食品药品检定研究院关键技术研究基金资助(GJJS-2022-4-2)。

摘　　要：目的 建立核磁共振定量与高效液相色谱联用技术(qNMR-HPLC)用于快速测定西洛他唑杂质Ⅰ校正因子。方法 西洛他唑与西洛他唑杂质Ⅰ的混合物溶于氘代二甲基亚砜(d-DMSO),取部分溶液使用核磁共振定量技术测定,另一部分溶液使用水-乙腈(60∶40)稀释后进行HPLC分析。使用qNMR中的响应信号与HPLC中峰面积计算西洛他唑杂质Ⅰ校正因子,同时使用HPLC标准曲线法测定西洛他唑杂质Ⅰ的校正因子。并制备含有残留溶剂的混合溶液模拟有残留溶剂干扰下,西洛他唑杂质Ⅰ含量赋值不准确时qNMR-HPLC联用与标准曲线法所得结果差异。结果 当西洛他唑与西洛他唑杂质Ⅰ含量赋值准确时,qNMR-HPLC法与HPLC标准曲线法测定西洛他唑杂质Ⅰ校正因子为1.74和1.76,与《中国药典》2020年版结果基本一致;当西洛他唑杂质Ⅰ中含有残留溶剂,含量赋值有误差时,qNMR-HPLC联用技术测定校正因子为1.72,计算结果不受含量是否准确的影响,而HPLC标准曲线测定的校正因子为2.01,与实际结果产生偏差。结论 与HPLC标准曲线法相比,qNMR-HPLC联用技术不受待测物含量是否准确以及称样量的影响,无须纯化制备纯度较高对照品,在杂质校正因子测定中具有明显优势。OBJECTIVE To establish a quantitative nuclear magnetic resonance coupled with high performance liquid chromatography(qNMR-HPLC) technique for the rapid determination of cilostazol impurity Ⅰ correction factor.METHODS The mixture of cilostazol and cilostazol impurity Ⅰ was dissolved in deuterated dimethyl sulfoxide.A portion of the solution was determined by qNMR,while the other portion of the solution was diluted with water-acetonitrile(60∶40) and analyzed by HPLC.The correction factor of cilostazol impurity Ⅰ was calculated with the response signals from qNMR and the peak areas from HPLC.The correction factor of cilostazol impurity Ⅰ was also determined by HPLC standard curve method.A mixed solution containing residual solvent was prepared to simulate the effect of solvents in determining correction factors.When the content of cilostazol impurity Ⅰ was inaccurately assigned due to residual solvent,difference between qNMR-HPLC method and standard curve method was compared.RESULTS When the contents of cilostazol and cilostazol impurity Ⅰ were assigned accurately,the correction factors for cilostazol impurity Ⅰ by qNMR-HPLC method and HPLC standard curve method were 1.74 and 1.76,respectively,which were basically consistent with the pharmacopoeial results.When cilostazol impurity Ⅰ contained residual solvents,and there was an error in the content assignment,the correction factor of the determination by the qNMR-HPLC technique was still 1.72,and the result was not affected by the accuracy of the content.While the correction factor of HPLC standard curve was 2.01,which was deviated from the actual results.CONCLUSION Compared with the HPLC standard curve method,the qNMR-HPLC coupling technique is independent of the accuracy of the content of the substance to be measured and the weighing volume,and does not require purification to prepare a high purity compound.qNMR-HPLC is a powerful tool in the determination of impurity correction factors.

关 键 词：核磁共振定量 高效液相色谱法 联用技术 西洛他唑 西洛他唑杂质Ⅰ 校正因子 

分 类 号：R917[医药卫生—药物分析学]