顶空气相色谱法测定石杉碱甲合成中间体中基因毒性杂质碘甲烷  

Determination of Genotoxic Impurity Iodomethane in Huperzine A Synthetic Intermediate by Head-space Gas Chromatography

作　　者：孙利荣 陈安 张晓妍 李娟 Sun Lirong;Chen An;Zhang Xiaoyan;Li Juan(Wanbangde Pharmaceutical Group Co.Ltd.,Zhejiang Wenling 317500,China)

机构地区：[1]万邦德制药集团有限公司,浙江温岭317500

出　　处：《中国药师》2022年第6期1095-1098,共4页China Pharmacist

摘　　要：目的:建立测定石杉碱甲合成中间体中的基因毒性杂质碘甲烷的顶空气相色谱分析法。方法:色谱柱为以100%二甲基聚硅氧烷为固定液的DB-1毛细管柱(30 m×0.53 mm,5μm),程序升温,进样口温度为200℃,检测器(FID)温度为250℃,顶空瓶平衡温度为55℃,平衡时间为30 min,定量环温度为65℃,传输线温度为80℃,分流比为5∶1,载气流量为2.0 ml·min^(-1),空气流量为300 ml·min^(-1),氢气流量为30 ml·min^(-1),尾吹气25 ml·min^(-1),顶空进样,进样体积为1.0 ml。结果:空白溶剂不影响样品测定,碘甲烷在2.9408-98.0274μg·ml^(-1)的浓度范围内呈现良好的线性关系(r=0.9996),平均回收率为104.06%(RSD=3.24%,n=9),定量限(LOQ)为2.9507μg·ml^(-1),检测限(LOD)为0.8852μg·ml^(-1)。结论:该方法专属性强,灵敏度及准确度高,耐用性良好,能够用于检测石杉碱甲合成中间体中基因毒性杂质碘甲烷,可为石杉碱甲合成工艺中碘甲烷的质量控制提供参考。Objective:To establish a head-space gas chromatography method for the determination of genotoxic impurity iodomethane in the synthetic intermediate of huperzine A.Methods:The gas chromatography was performed on a DB-1 capillary column(30 m×0.53 mm,5μm)with 100%dimethyl polysiloxane as the fixative liquid and with programed heating,the temperature of injection port was at 200℃,the detector was fame ionization detector(FID)with temperature at 250℃,the equilibrium temperature of the headspace bottle was set at 55℃,the equilibrium time was 30 min,the quantitative loop temperature was at 65℃,the temperature of transmission line was set at 80℃,the split ratio was 5∶1,the flow rate of carrier gas was 2.0 ml·min^(-1),the flow rate of air was 300 ml·min^(-1),the flow rate of hydrogen was 30 ml·min^(-1),the flow rate of makeup gas was 25 ml·min^(-1),and the volume of headspace injection was 1.0 ml.Results:The blank solvent did not affect the determination of samples,and their linear ranges were 2.9408-98.0274μg·ml^(-1)(r=0.9996).The average recovery was 104.06%(RSD=3.24%,n=9),the LOQ was 2.9507μg·ml^(-1),and the LOD was 0.8852μg·ml^(-1).Conclusion:This method has strong specificity,high sensitivity and promising accuracy with great durability.It can be used to determine genotoxic impurity iodomethane in the synthetic intermediate of huperzine A,which provides reference for the quality control of iodomethane in the synthesis process of huperzine A.

关 键 词：顶空气相色谱法 石杉碱甲 基因毒性杂质 方法学验证 碘甲烷 

分 类 号：TQ460.72[医药卫生—药物分析学]