甘磷酸胆碱原料药中3种遗传毒性杂质含量测定方法的建立  

Method Establishment of Content Determination of Three Toxic Impurities in Glycerophosphorylcholine Raw Materials

作　　者：张伟奇 王倩 何燕 王雪芹[2] ZHANG Weiqi;WANG Qian;HE Yan;WANG Xueqin(Henan Provincial Food and Drug Evaluation and Inspection Center,Zhengzhou 450000,China;Henan Provincial Institute for Food and Drug Control,Zhengzhou 450008,China)

机构地区：[1]河南省食品药品审评查验中心,郑州450000 [2]河南省食品药品检验所,郑州450008

出　　处：《中国药房》2021年第21期2631-2634,共4页China Pharmacy

基　　金：河南省市场监督管理局科技计划项目(No.2020sj27)。

摘　　要：目的:建立气-质联用(GC-MS)法同时测定甘磷酸胆碱原料药中环氧氯丙烷、缩水甘油、3-氯-1,2-丙二醇等3种遗传毒性杂质的含量。方法:以4批甘磷酸胆碱原料药为检测样品。色谱柱为ZB-WAXplusTM;进样口温度为200℃;进样方式为不分流进样;载气为氦气(He),恒流模式;程序升温为初始温度30℃保持1min,然后以30℃/min的速率升温至220℃并保持5min;进样量为1μL。离子源为电子轰击源(EI),电离电压为70eV,离子源温度为200℃;质谱传输接口温度为250℃;质谱监测模式为选择离子(SIM);检测特征离子为环氧氯丙烷[质荷比(m/z)49、57、62]、缩水甘油(m/z31、43、44)、3-氯-1,2-丙二醇(m/z44、61、79);溶剂延迟时间为3min。结果:环氧氯丙烷、缩水甘油、3-氯-1,2-丙二醇检测的质量浓度线性范围分别为29.86~746.48、172.91~922.18、21.18~211.85ng/mL(r均大于0.9990);检测限分别为19.91、115.27、10.59ng/mL;定量限分别为29.86、172.91、21.18ng/mL;精密度(n=6)、重复性(n=6)、稳定性(室温放置12h,n=8)试验的RSD均小于10%;平均加样回收率分别为93.88%、91.45%、91.86%,RSD分别为5.10%、3.10%、2.49%(n=9)。在4批甘磷酸胆碱原料药中,均未检出上述3种遗传毒性杂质。结论:建立的GC-MS法简单高效、准确度高、重复性好,可用于同时测定甘磷酸胆碱原料药中环氧氯丙烷、缩水甘油、3-氯-1,2-丙二醇等3种遗传毒性杂质的含量。OBJECTIVE:To establish GC-MS method for the content determination of three toxic impurities in glycerophosphorylcholine raw materials,such as epichlorohydrin,glycidyl,3-chloro-1,2-propanediol.METHODS:Four batches of glycerophosphorylcholine raw materials were used as test samples.The determination was performed on ZB-WAXplus TM column,and the injector temperature was 200℃;the sample injection adopted splitless injection mode,using helium(He)as carrier gas,in constant current mode;the temperature program for the column was initially heating at 30℃for 1 min,rising to 220℃at a speed of 30℃/min then remaining 5 min.The ion source was electrospray ion source(EI),the ion source temperature was 200℃,and the ionization energy was 70 eV;transmission interface temperature was 250℃,and mass spectrum monitoring mode was selected ion(SIM).Detection ions were epichlorhydrin[mass charge ratio(m/z)49,57,62],glycidyl(m/z 31,43,44),3-chloro-1,2-propanediol(m/z 44,61,79).The solvent delay time was 3 min.RESULTS:The linear range of epichlorhydrin,glycidyl and 3-chloro-1,2-propanediol were 29.86-746.48,172.91-922.18,21.18-211.85 ng/mL,respectively(all r>0.9990).The detection limits were 19.91,115.27,10.59 ng/mL,respectively.The limits of quantitation were 29.86,172.91,21.18 ng/mL,respectively.RSDs of precision(n=6),reproducibility(n=6)and stability(placed at room temperature for 12 h,n=8)tests were all lower than 10%.The average recoveries were 93.88%,91.45%,91.86%,and RSDs were 5.10%,3.10%,2.49%(n=9),respectively.In the 4 batches of glycerophosphorylcholine raw materials,three toxic impurities were all not detected.CONCLUSIONS:Established GC-MS method is simple,efficient,accurate and repeatable,and it can be used to determine the contents of three toxic impurities in glycerophosphorylcholine raw materials,such as epichlorohydrin,glycidyl,3-chloro-1,2-propanediol.

关 键 词：气-质联用法 甘磷酸胆碱 环氧氯丙烷 缩水甘油 3-氯-1 2-丙二醇 

分 类 号：R917[医药卫生—药物分析学]