摘要
目的:建立厄贝沙坦原料药和氯沙坦钾原料药中5-[4'-(叠氮甲基)-[1,1'-联苯]-2-基]-1H-四氮唑(MB-X),4'-叠氮甲基-[1,1'-联苯]-2-氰基(AZBC)和5-[4'-[(5-(叠氮甲基)-2-丁基-4-氯-1H-咪唑-1-基)甲基]-[1,1'-联苯]2-基]-1H-四唑(LADX)这3种叠氮类基因毒性杂质的超高效液相色谱-串联(UPLCMS/MS)三重四级杆质谱的检测方法。方法:ACQUITY UPLC HSS T3(100 mm×2.1 mm,1.8μm)色谱柱;0.1%甲酸水溶液为流动相A,0.1%甲酸的甲醇溶液为流动相B,梯度洗脱;流速为0.35 mL·min-1,柱温为50℃;采用大气压化学离子源(APCI)正/负离子扫描,多反应监测(MRM)模式对3种基因毒性杂质同时进行定量检测。结果:3种杂质在0.5~100 ng·mL^(-1)范围内具有良好的线性关系;检测限分别为0.05,0.03,0.02 ng·mL^(-1),定量限分别为0.15,0.11,0.08 ng·mL^(-1);3种杂质在厄贝沙坦原料药中,低、中、高3个浓度的加样回收率(n=3)范围为94.5%~103.5%,相对标准偏差(RSD)<3.88%;在氯沙坦钾原料药中,低、中、高3个浓度的加样回收率(n=3)范围为93.8%~100.9%,RSD<4.25%。结论:该方法灵敏度高、专属性强,可用于测定厄贝沙坦原料药和氯沙坦钾原料药中3种叠氮类基因毒性杂质,为厄贝沙坦和氯沙坦钾的质量控制提供技术支持。
Objective:To eatablish a UPLC-MS/MS method for determination of three azide-type genotoxics,5-(4'-(azidomethyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole(MB-X),4'-(azidomethyl)-[1,1'-bihenyl]-2-carbonitrile(AZBC),and 5-(4'-((5-azido-2-butyl-4-chloro-1H-imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole(LADX),in active pharmaceutical ingredients(API)of irbesartan and losartan potassium.Methods:The separation was performed on a ACQUITY UPLC HSS T3 column(100 mm×2.1 mm,1.8μm)with the mobile phases consisting of 0.1%formic acid aqueous solution(mobile phase A)and 0.1%formic acid methanol solution(mobile phase B)using a gradient elution at a flow rate of 0.35 mL·min-1.The column temperature was set at 50℃.Multiplereaction monitoring(MRM)was performed on a triple quadripole mass spectrometer equipped with a APCI source in positive/negative mode.Results:the calibration curve was linear for three compounds in the range of 0.5~100 ng·mL^(-1).The recoveries(n=3)in irbesartan of low,middle,high concentration-spiked samples are 94.5%~103.5%with RSD < 3.88%.The recoveries( n = 3) in losartan potassium of low,middle,high concentration-spiked samples are93.8% ~ 100.9% with RSD < 4.25%.The limits of detection are 0. 05,0. 03,0. 02 ng·mL^(-1) and the limits ofquantification are 0.15,0.11,0.08 ng·mL^(-1),respectively.Conclusion: The method is sensitive and accurate,which is applicable for quantification of three azide-type genotoxic impurities in irbesartan API and losartan potassiumAPI.The method can provide reference for quality control of irbesartan and losartan potassium.
作者
黄海伟
袁松
张龙浩
何兰
张庆生
HUANG Hai-wei;YUAN Song;ZHANG Long-hao;HE Lan;ZHANG Qing-sheng(Key Labboratory for Quality Research and Evaluation of Chemical Drugs of NMPA,National Institute for Food and Drug Control,Beijing 102629,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2023年第7期742-746,共5页
Chinese Journal of New Drugs
