气相色谱-质谱联用法测定拉洛他赛原料中三氟甲磺酸乙酯基因毒杂质

Determination by Gas Chromatography-mass Spectrometry Genotoxic Impurities of Ethyl Trifluoromethanesulfonate in Raw Materials of Larotaxel

目的建立气相色谱-质谱联用法,测定拉洛他赛原料中基因毒杂质三氟甲磺酸乙酯。方法采用6%氰丙基苯基和94%二甲基聚硅氧烷为固定相的毛细管柱(DB-624,30 m×0.25 mm×1.4μm),EI源,以起始温度为50℃,维持6 min,以30℃/min的速率升温至230℃,250℃下运行3 min;流速为1.0 mL·min^(-1)。结果三氟甲磺酸乙酯检测限为1.81ppb,定量限为6.15ppb,三氟甲磺酸乙酯在3.65~584.62 ng·mL^(-1)浓度范围内线性关系良好(r=0.9998),方法回收率(n=9)均在95.4%~111.4%范围内,RSD<5.6%。结论方法简便、准确,灵敏度高,专属性强,可用于拉洛他赛原料中三氟甲磺酸乙酯基因毒杂质的测定。

OBJECTIVE To establish a gas chromatography-mass spectrometry method for the determination of ethyl trifluoromethanesulfonate,a genotoxic impurity,in raw materials of lalotaxel.METHODS A capillary column(DB-624,30 m×0.25 mm×1.4μm)with 6%cyanopropylphenyl and 94%dimethylpolysiloxane as the stationary phase was used,the EI source was used,and the initial temperature was 50℃,maintained for 6 minutes,heated to 230℃at a rate of 30℃per minute,and operated at 250℃for 3 minutes;the flow rate was 1.0 mL·min^(-1).RESULTS The detection limit of ethyl trifluoromethanesulfonate was 1.81ppb,and the limit of quantification was 6.15ppb.The linear relationship of ethyl trifluoromethanesulfonate in the concentration range of 3.65-584.62 ng·mL^(-1)was good(r=0.9998),and the method was recovered.The rate of quantification(n=9)was in the range of 95.4%-111.4%,the RSD was less than 5.6%.CONCLUSION The method is simple,accurate,sensitive and specific,and can be used for the determination of ethyl trifluoromethanesulfonate genotoxic impurities in larotaxel raw materials.