摘要
建立测定马昔腾坦原料药中潜在基因毒性杂质正丙氨基磺酸含量的UPLC-Q-TOF-MS方法。采用Waters CORTECS®C_(18)(4.6 mm×50 mm,2.7µm)色谱柱,以0.1%氨水(A)和乙腈(B)为流动相,流速为0.4 mL·min^(-1),梯度洗脱程序:0~4 min,90%A→20%A;4~5 min,20%A;5.1~9 min,90%A;带有安捷伦喷射流技术的电喷雾离子源(ESI),负离子采集模式,监测模式为选择离子监测(SIM),监测离子(m/z)为138.0,外标法测定。正丙氨基磺酸浓度在1.99~299.10 ng·mL^(-1)内线性关系良好(r=0.9988),检出限(LOD):0.50 ng·mL^(-1),定量限(LOQ):1.99 ng·mL^(-1)。该方法选择性强,灵敏度高,快速高效,能准确测定马昔腾坦原料药中潜在基因毒性杂质正丙氨基磺酸的含量。
An UPLC-Q-TOF-MS method was established for content determination of n-propyl sulfamic acid,a potential genotoxic impurity in active pharmaceutical ingredient of macitentan.A Waters CORTECS®C_(18)(4.6 mm×50 mm,2.7µm)column was adopted,the mobile phase consisted of 0.1%ammonia(A)and acetonitrile(B)at a flow rate of 0.4 mL·min^(-1) by gradient elution:0 to 4 min,90%A→20%A;4 to 5 min,20%A;5.1 to 9 min,90%A.The detection was accomplished by electrospray ion source with Agilent Jet Steam Technology(ESI)in negative mode using selected ion monitoring(SIM),the optimized mass ion-pairs for quantitated was 138.0(m/z),external standard method was used.The linear range of n-propyl sulfamic acid was from 1.99 to 299.10 ng·mL^(-1)(r=0.9988),the limit of detection(LOD)was 0.50 ng·mL^(-1),and the limit of quantitation(LOQ)was 1.99 ng·mL^(-1).The method is selective and sensitive,rapid and efficient,can accurately determine the potential genotoxic impurity n-propylaminosulfonic acid in active pharmaceutical ingredient of macitentan.
作者
姚福友
张利娜
YAO Fuyou;ZHANG Lina(Zhejiang Xianfeng Technology Group Co.,Ltd.,Zhejiang Linhai 317021;Zhejiang Weifeng Pharmaceutical Co.,Ltd.,Zhejiang Linhai 317016,China)
出处
《广州化工》
2025年第16期134-136,172,共4页
GuangZhou Chemical Industry
