摘要
目的建立气相色谱-质谱联用(GC-MS)法同时测定福多司坦原料药中四种遗传毒性杂质3-氯-1-丙醇、1,3-二氯丙烷、3-氯丙酸乙酯和氯丙基羟丙基醚。方法以氯苯为内标物,采用Agilent J&W VF-WAXms色谱柱(30 m×0.25 mm,0.5μm),程序升温;离子源温度230℃,四极杆温度150℃,进样口温度220℃,流速1.0 mL·min^(-1),分流比2∶1;在离子选择(SIM)模式下,监控m/z 58.1、76.0、91.0、58.1和107.9离子进行检测。结果3-氯-1-丙醇、1,3-二氯丙烷、3-氯丙酸乙酯和氯丙基羟丙基醚四种杂质分别在0.0009~0.8820μg·mL^(-1)、0.0022~0.8740μg·mL^(-1)、0.0090~0.8920μg·mL^(-1)和0.0166~0.8300μg·mL^(-1)范围内呈良好的线性关系(R2≥0.9999,n=5),检测限为0.2640~4.980 ng·mL^(-1),定量限为0.8800~16.60 ng·mL^(-1),平均回收率为89.2%~95.5%,重复性良好(RSD=0.30%~6.63%)。结论该方法可作为福多司坦原料药遗传毒性杂质的质量控制方法。
Objective To establish a gas chromatography-mass spectrometry(GC-MS)method for the determination of genotoxic impurities 3-chloro-1-propanol,1,3-dichloropropane,ethyl 3-chloropropionate and chloropropyl hydroxypropyl ether in raw material of fudosteine.Methods Chlorobenzene was choosen as the internal standard.Efficient chromatographic separations were achieved on an Agilent J&W VF-WAXms column(30 m×0.25 mm,0.5μm)by using programmed temperature with ion source temperature 230℃,MSD temperature 150℃and injector temperature 220℃.The flow rate was set at 1.0 mL·min-1 with split ratio 2:1.In SIM mode,m/z 58.1,76.0,91.0,58.1 and 107.9 ions were chosen as quantitative channels.Results 3-chloro-1-propanol,1,3-dichloropropane,ethyl 3-chloropropionate and chloropropyl hydroxypropyl ether showed good linear relationships within the ranges of 0.0009-0.8820μg·mL^(-1),0.0022-0.8740μg·mL^(-1),0.0090-0.8920μg·mL^(-1)and 0.0166-0.8300μg·mL^(-1),respectively(R 2≥0.9999,n=5).The limits of detection were 0.2640-4.980 ng·mL^(-1)and the limits of quantification were 0.8800-16.60 ng·mL^(-1).The average recoveries were 89.2%to 95.5%,and the precision was well performed(RSD=0.30%-6.63%).Conclusion This method is applicable for the quality control of the genotoxic impurities determination of fudosteine.
作者
刘昊昆
王慧嘉
侯霞
许华容
李清
LIU Haokun;WANG Huijia;HOU Xia;XU Huarong;LI Qing(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2023年第11期1432-1438,共7页
Journal of Shenyang Pharmaceutical University
基金
沈阳药科大学大学生创新创业训练计划项目(202210163009)。
