张伟奇　王倩　何燕　王雪芹

中图分类号 R917 文献标志码 A 文章编号 1001-0408（2021）21-2631-04

DOI 10.6039/j.issn.1001-0408.2021.21.12

摘 要 目的：建立氣-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1 min，然后以30 ℃/min的速率升温至220 ℃并保持5 min;进样量为1 μL。离子源为电子轰击源（EI），电离电压为70 eV，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/z 31、43、44）、3-氯-1，2-丙二醇（m/z 44、61、79）;溶剂延迟时间为3 min。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、21.18～211.85 ng/mL（r均大于0.999 0）;检测限分别为19.91、115.27、10.59 ng/mL;定量限分别为29.86、172.91、21.18      ng/mL;精密度（n=6）、重复性（n=6）、稳定性（室温放置12 h，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。

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

ABSTRACT   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-WAXplusTM 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>0.999 0）. 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.

KEYWORDS   GC-MS method; Glycerophosphorylcholine; Epichlorhydrin; Glycidyl; 3-chloro-1，2-propanediol

甘磷酸膽碱又称甘磷酰胆碱、甘油卵磷脂，是一种人体内天然存在的水溶性磷脂代谢产物，具有提高记忆力、防衰老、降血脂、保肝、健脑等多种功效[1-2]。3-氯-1，2-丙二醇又称3-氯-1，2-二羟基丙烷，是合成甘磷酸胆碱的起始物料，其可能对人体产生肝肾毒性、免疫毒性、遗传毒性、生殖毒性，并具有致癌性[3-5]。环……