GC-MS法测定甲磺酸达比加群酯中的致突变杂质  

Determination of the contents of mutagenic impurity in Dabigatran Etexilate Mesylate by GC-MS

作　　者：柏建学 柴发永 范锋 BAI Jianxue;CHAI Fayong;FAN Feng(Shandong Center for Food and Drug Evaluation&Inspection,Jinan 250014,China;Cisen Pharmaceutical Co.,Ltd.,Jining 272073,China)

机构地区：[1]山东省食品药品审评查验中心,山东济南250014 [2]辰欣药业股份有限公司,山东济宁272073

出　　处：《药学研究》2021年第10期652-655,共4页Journal of Pharmaceutical Research

摘　　要：目的建立一种气相色谱-质谱联用法(GC-MS)同时测定甲磺酸达比加群酯中甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯的方法。方法采用DB-624色谱柱(30 m×0.25 mm,1.4μm);程序升温:起始温度100℃,以15℃·min^(-1)的速率升温至200℃,再以25℃·min^(-1)的速率升温至240℃;进样口温度为220℃,载气为氦气,流速为1.0 mL·min^(-1),进样量为2.0μL。采集模式为选择离子监测(SIM),离子源温度为230℃。通过内标法进行计算。结果3种甲磺酸酯之间的分离度均大于2.0,甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯的线性回归方程分别为Y=0.0130X+0.0524(r=0.9990)、Y=0.0249X+0.0633(r=0.9993)、Y=0.0188X+0.0906(r=0.9985),均在5.0~120.0 ng·mL^(-1)浓度范围内线性关系良好。检出限为1.5 ng·mL^(-1)(0.15 ppm),定量限为5 ng·mL^(-1)(0.5 ppm)。甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯的平均回收率分别为96.28%、97.91%和95.87%,RSD分别为2.83%、2.93%和1.73%。结论本方法简便、快速、准确、专属性强、灵敏度高,适用于甲磺酸达比加群酯中3种甲磺酸酯的检测。Objective To establish a method for determination of MMS,EMS and IMS in Dabigatran Etexilate Mesylate by GC-MS.Methods The analysis was carried on an DB-624 column(30 m×0.25 mm,1.4μm).The GC oven temperature was programmed with an initial temperature of 100℃,increasing to 200℃by 15℃·min^(-1),then increasing to 240℃by 25℃·min^(-1).The temperature of the injection port and interface was set at 220℃.Helium was used as the carrier gas;the flow rate was 1.0 mL·min^(-1),and the volume of the injection was 2.0μL.Data acquisition was performed with SIM,and the temperature of the ion source was set at 230℃.Calculated by internal standard method.Results The resolutions of the three mathane sulfonates were greater than 2.0.Linear regression equation of MMS,EMS and IMS was Y=0.0130X+0.0524(r=0.9990),Y=0.0249X+0.0633(r=0.9993),and Y=0.0188X+0.0906(r=0.9985).The linearitis of all were good in the range of 5.0~120.0 ng·mL^(-1).The limit of detection was 1.5 ng·mL^(-1)(0.15 ppm),and the limit of quantification was 5 ng·mL^(-1)(0.5 ppm),respectively.The extractive recovery of MMS,EMS and IMS was 96.28%,97.91%and 95.87%,and the RSD was 2.83%,2.93%and 1.73%,respectively(n=9).Conclusion The method was proved to be simple,accurate,rapid,high sensitivity and good selectivity,and suitable for the determination of the three mathane sulfonates in Dabigatran Etexilate Mesylate.

关 键 词：甲磺酸达比加群酯 甲磺酸甲酯 甲磺酸乙酯 甲磺酸异丙酯 气相色谱-质谱联用法 

分 类 号：R927.1[医药卫生—药学]