摘要
目的:建立HPLC-Q-Orbitrap方法测定盐酸法舒地尔中的基因毒性杂质5-异喹啉磺酸甲酯和5-异喹啉磺酸乙酯。方法:采用Thermo Scientific Hypersil GOLD C8色谱柱(4.6 mm×150 mm,3μm),以乙腈(A)-0.1%甲酸水溶液(B)为流动相,梯度洗脱,流速0.9 mL·min^(-1),柱温30℃;以Q-Orbitrap高分辨质谱检测,采用ESI离子源,正离子模式,Full MS-SIM模式扫描,扫描范围m/z 223~239。采用提取离子流色谱定量,分别选择m/z224.03759(质量偏差<5×10-6)和m/z 238.05324(质量偏差<5×10-6)作为5-异喹啉磺酸甲酯和5-异喹啉磺酸乙酯的定量离子。结果:5-异喹啉磺酸甲酯和5-异喹啉磺酸乙酯质量浓度在1.0~30 ng·m L^(-1)范围内线性关系良好(r分别为0.9983、0.9990);检测下限分别为0.66、0.30μg·g^(-1),定量下限分别为2.0、1.0μg·g^(-1);加样回收率(n=6)分别为95.4%、97.1%,RSD分别为2.1%、1.9%。6批样品中均未检出5-异喹啉磺酸甲酯和5-异喹啉磺酸乙酯。结论:本方法简便、快速、准确、灵敏,可用于盐酸法舒地尔的质量控制。
Objective:To establish an HPLC-Q-Orbitrap method to determine the contents of genotoxic impurities methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate in fasudil hydrochloride.Methods:The separation was performed on a Thermo Scientific Hypersil GOLD C8 column(4.6 mm×150 mm,3μm)using the mobile phase consisting of acetonitrile(mobile phase A)and 0.1%formic acid aqueous solution(mobile phase B)by gradient elution at a flow rate of 0.9 mL·min^(-1).The column temperature was set at 30℃.The analytes were detected by Q-Orbitrap high resolution mass spectrometry with ESI source in positive mode.The detection was achieved in Full MS-SIM mode,and the scan range was set at m/z 223-239.The extracted ion chromatograms were used for the quantitation,selecting m/z 224.03759(mass tolerance<5×10^(-6))and m/z 238.05324(mass tolerance<5×10^(-6))as the quantitative ions of methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate,respectively.Results:Methyl isoquinoline-5-sulfonate and ethyl isoquinoline-5-sulfonate showed good linear relationships within the range of 1.0-30 ng·mL^(-1)(r=0.9983 and 0.9990,respectively).The limit of detection and limit of quantification for methyl isoquinoline-5-sulfonate was 0.66μg·g^(-1) and 2.0μg·g^(-1),respectively.The limit of detection and limit of quantification for ethyl isoquinoline-5-sulfonate was 0.30μg·g^(-1) and 1.0μg·g^(-1),respectively.The spike recoveries(n=6)of the two compounds were 95.4%and 97.1%,with RSD of 2.1%and 1.9%,respectively.The two genotoxic impurities were not detected in 6 batches of samples.Conclusion:The established method is simple,rapid,accurate and sensitive,and can be used for the quality control of fasudil hydrochloride.
作者
刘暘
李剑峰
李宁
陈云建
刘世成
杨兆祥
LIU Yang;LI Jian-feng;LI Ning;CHEN Yun-jian;LIU Shi-cheng;YANG Zhao-xiang(KPC Pharmaceuticals,Inc,Kunming 650100,China;Dali University,Dali 671000,China;Yunnan University of Traditional Chinese Medicine,Kunming 650500,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2021年第1期154-159,共6页
Chinese Journal of Pharmaceutical Analysis
基金
云南省人力资源和社会保障厅第三批博士后定向培养资助。
