摘要
目的:建立超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定阿加曲班中4个基因毒性杂质:3-甲基-8-喹啉磺酸、3-甲基-8-喹啉磺酸甲酯、3-甲基-8-喹啉磺酸乙酯、3-甲基-8-喹啉磺酰氯。方法:采用Waters ACQUITY UPLC BEH C18(100 mm×2.1 mm,1.7μm)色谱柱;以0.1%甲酸水溶液为流动相A,乙腈为流动相B进行线性梯度洗脱;流速0.2 mL·min^-1;采用ESI离子源正离子模式,多反应监测模式下,以外标法对4个基因毒性杂质同时进行定量测定。结果:除3-甲基-8-喹啉磺酰氯外,其他3个基因毒性杂质质量浓度在0.125~500 ng·mL^-1范围内线性关系良好;低、中、高3个浓度的加样回收率(n=3)范围为91.5%~104.2%,RSD范围为0.15%~4.6%;检测下限范围为0.042~1.667 ng·mL^-1,定量下限范围为0.125~5.000 ng·mL^-1。样品中均未检出杂质。结论:本方法操作简便,结果可靠,经方法学验证,可用于阿加曲班中4个基因毒性杂质的同时检测。
Objective:To establish a UPLC-MS/MS analytical method for the determination of genotoxic impurities(3-methyl-8-quinoline sulfonic acid,3-methyl-8-methyl quinolinesulfonate,3-methyl-8-ethyl quinolinesulfonate,and 3-methyl-8-quinolinesulphonyl chloride)in argatroban.Methods:The separation was performed on a Waters ACQUITY UPLC BEH C18(100 mm×2.1 mm,1.7μm)with the mobile phase consisting of 0.1%formic acid aqueous solution(mobile phase A)and acetonitrile(mobile phase B)by gradient elution at a flow rate of 0.2 mL·min^-1.Multiple reaction monitoring(MRM)was performed on a triple quadrupole mass spectrometer equipped with a ESI source in the positive mode.Results:Except for 3-methyl-8-quinolinesulphonyl chloride,the calibration curve was linear for other compounds in the range of 0.125-500 ng·mL^-1.The recoveries(n=3)of low,middle and high adding concentrations were 91.5%^-104.2%,RSD were 0.15%-4.6%.The limit of detection was 0.042^-1.667 ng·mL^-1,and the limit of quantification was 0.125-5.000 ng·mL^-1.No impurities were detected in the samples.Conclusion:This established method is simple,rapid and reliable,which is applicable for quantifications of four genotoxic impurities in argatroban.
作者
勾新磊
赵铁禅
赵婷
张梅
刘伟丽
高峡
赵新颖
胡光辉
张秀亭
GOU Xin-lei;ZHAO Tie-chan;ZHAO Ting;ZHANG Mei;LIU Wei-li;GAO Xia;ZHAO Xin-ying;HU Guang-hui;ZHANG Xiu-ting(Beijing Key Laboralory of Organic Materials Testing Technology&Quality Evaluation,Beijing Centre for Physical and Chemical Analysis,Beijing 100089,China;Beijing Youcare Kechuang Pharmaceutical Technology Co.,Ltd.,Beijing 10076,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第11期2059-2063,共5页
Chinese Journal of Pharmaceutical Analysis
基金
北京市自然科学基金-北京市科学技术研究院联合资助项目(L160005)
北京市科学技术研究院高水平创新团队计划(HIT201902)
北京市科学技术研究院北科萌芽计划(BGS201904)
