| 引用本文: | 曹琳,罗淑青,章燕,陈军,孙春业,赖丛芳,钱江.LC-QQQ-MS/MS分析苯磺酸氨氯地平中痕量苯磺酸酯类基因毒性杂质[J].中国现代应用药学,2020,37(11):1296-1300. |
| CAO Lin,LUO Shuqing,ZHANG Yan,CHEN Jun,SUN Chunye,LAI Congfang,QIAN Jiang.Determination of Trace Genotoxic Impurities of Benzenesulfonate Esters in Amlodipine Besilate by LC-QQQ-MS/MS[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(11):1296-1300. |
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| LC-QQQ-MS/MS分析苯磺酸氨氯地平中痕量苯磺酸酯类基因毒性杂质 |
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曹琳1, 罗淑青1, 章燕1, 陈军1, 孙春业2, 赖丛芳3, 钱江4
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1.宁波市药品检验所, 浙江 宁波 315048;2.安捷伦科技(中国)有限公司上海第一分公司, 上海 200080;3.安捷伦科技(中国)有限公司, 北京 100102;4.浙江医药高等专科学校, 浙江 宁波 315100
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| 摘要: |
| 目的 建立LC-QQQ-MS/MS分析测定苯磺酸氨氯地平中痕量苯磺酸酯类基因毒性杂质苯磺酸甲酯、苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯的检测方法。方法 采用Agilent Zorbax SB-C18（3.0 mm×100 mm，1.8 μm）色谱柱，以水（含5 mmol·L-1甲酸铵和0.1%甲酸）和甲醇（含5 mmol·L-1甲酸铵和0.1%甲酸）为流动相，梯度洗脱，流速0.4 mL·min-1，电喷雾离子化（ESI），正离子模式下MRM采集。结果 苯磺酸甲酯定量下限为20 ng·mL-1，苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯定量下限为1 ng·mL-1；方法精密度良好，保留时间和峰面积RSD均<5%（n=10）；苯磺酸甲酯在20~1 000 ng·mL-1，苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯在1~1 000 ng·mL-1内呈良好的线性关系，r≥0.998；方法准确度良好，平均加样回收率（n=10）分别为99.77%，100.19%，94.21%和92.43%。5个不同厂家生产的苯磺酸氨氯地平中苯磺酸甲酯的含量均-1），苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯的含量均-1）。结论 该方法可用于苯磺酸氨氯地平中痕量基因毒性杂质苯磺酸甲酯、苯磺酸乙酯、苯磺酸丙酯和苯磺酸异丙酯含量的检测分析。 |
| 关键词: 苯磺酸氨氯地平 基因毒性杂质 苯磺酸甲酯 苯磺酸乙酯 苯磺酸丙酯 苯磺酸异丙酯 LC-QQQ-MS/MS |
| DOI：10.13748/j.cnki.issn1007-7693.2020.11.003 |
| 分类号:R971.101 |
| 基金项目:国家药品监督管理局仿制药评价关键技术重点实验室开放基金项目（GZYZF2020002） |
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| Determination of Trace Genotoxic Impurities of Benzenesulfonate Esters in Amlodipine Besilate by LC-QQQ-MS/MS |
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CAO Lin1, LUO Shuqing1, ZHANG Yan1, CHEN Jun1, SUN Chunye2, LAI Congfang3, QIAN Jiang4
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1.Ningbo Institute for Drug Control, Ningbo 315048, China;2.Agilent Technologies(China) Co., Ltd., Shanghai No.1 Branch, Shanghai 200080, China;3.Agilent Technologies(China) Co., Ltd., Beijing 100102, China;4.Zhejiang Pharmaceutical College, Ningbo 315100, China
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| Abstract: |
| OBJECTIVE To establish an LC-QQQ-MS/MS method for the determination of trace genotoxic impurities of benzenesulfonate esters including methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate in amlodipine besilate. METHODS Agilent Zorbax SB-C18(3.0 mm×100 mm, 1.8 μm) analytical column was used for the separation with a mobile phase of water(5 mmol·L-1 ammonium formate and 0.1% formic acid) and methanol (5 mmol·L-1 ammonium formate and 0.1% formic acid) at a flow rate of 0.4 mL·min-1 in gradient elution mode. The method was developed at ESI(+) with MRM mode. RESULTS The LOQ of methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were 20, 1, 1, 1 ng·mL-1, respectively. The method had good precision, the RSD of retention time and peak area were both <5% for the four target compounds(n=10). The linearity range of methyl benzenesulfonate was 20-1 000 ng·mL-1, the linearity ranges of ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were all 1-1 000 ng·mL-1, with the excellent correlation coefficient(r) ≥ 0.998. The method had good accuracy, average recoveries(n=10) were 99.77%, 100.19%, 94.21% and 92.43%, respectively. The contents of methyl benzenesulfonate in amlodipine besylate samples from five different manufacturers were all -1), the contents of ethyl benzenesulfonate, propyl benzenesulfonate and isopropyl benzenesulfonate were all -1). CONCLUSION The established method can be applied to the determination of trace genotoxic impurities of benzenesulfonate esters (methyl benzenesulfonate, ethyl benzenesulfonate, propyl benzenesulfonate, isopropyl benzenesulfonate) in amlodipine besylate. |
| Key words: amlodipine besilate genotoxic impurities methyl benzenesulfonate ethyl benzenesulfonate propyl benzenesulfonate isopropyl benzenesulfonate LC-QQQ-MS/MS |
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