HS-GC-MS法测定头孢氨苄原料药中基因毒性杂质特戊酰氯残留量  

Determination of Residues of Genotoxic Impurity Pivaloyl Chloride in Cefalexin API by HS-GC-MS

作　　者：李小聪 廖宗权 谢瑶[1] 周妮 曹晓洲 罗楠 孙志伟[1] Li Xiaocong;Liao Zongquan;Xie Yao;Zhou Ni;Cao Xiaozhou;Luo Nan;Sun Zhiwei(Hubei Three Gorges Polytechnic,Yichang 443000,China;Yichang Humanwell Pharmaceutical Co.,Ltd.,Yichang 443003,China)

机构地区：[1]湖北三峡职业技术学院,湖北宜昌443000 [2]宜昌人福药业有限责任公司,湖北宜昌443003

出　　处：《广东化工》2024年第17期155-157,共3页Guangdong Chemical Industry

基　　金：宜昌市科技局自然科学研究项目(A24-3-032);湖北省中华职业教育社课题研究项目(HBZJ2024182)。

摘　　要：目的:建立并验证了顶空气相色谱-质谱(HS-GC-MS)法测定头孢氨苄原料药中的基因毒性杂质特戊酰氯的残留量。方法:采用HP-1MS UI毛细管柱(30 m×0.25 mm,0.5μm)色谱柱,载气为He,流速为1 ml.min^(-1);进样口温度200℃,定量环温度80℃,顶空平衡温度70℃,传输线温度90℃,程序升温;质谱采用EI源,质谱传输线温度为250℃;定量测定采用选择离子(SIM)模式,特戊酸乙酯m/z 57.1。以4批头孢氨苄原料药为测定对象,测定其基因毒性杂质特戊酰氯的残留量。结果:特戊酸乙酯与相邻色谱峰之间的分离度良好,且在浓度范围50.170 ng.mL^(-1)~501.695 ng·mL^(-1)内,其与峰面积线性关系良好(r=0.995),其定量限和检测限分别为24.945 ng·mL^(-1)和12.473 ng·m L^(-1),平均加样回收率为110%,RSD为6.0%(n=9)。结论:该法灵敏度高、专属性强,可用于测定头孢氨苄原料药中基因毒性杂质特戊酰氯的残留量。Objective:To establish a specific HS-GC-MS method to determination of residues of genotoxic impurity pivaloyl chloride in Cefalexin API.Methods:The separation was performed on a HP-1MS UI capillary column(30 m×0.25 mm,0.5μm)in a temperature rising program.The carrier gas was helium with flow rate of 1 mL·min-1.The inlet temperature was 200℃,the headspace equilibrium temperature was 70℃,the quantitative ring temperature was 80℃,and the headspace transmission line temperature was 90℃.The sample was ionized by electron ionization.The ion source temperature was 230℃,the quadrupole temperature was 150℃,and the MSD transmission line temperature was 250℃.Detection were performed by mass spectrometry in selective ion monitoring mode with m/z 57.1 for ethyl pivalate.The genotoxic impurity pivaloyl chloride was detected in 4 batches of Cefalexin API following based on the conditions.Results Ethyl pivalate and adjacent chromatographic peaks were separated well and showed good linearity at 50.170 ng·mL^(-1)~501.695 ng·mL^(-1)(r=0.995).The limits of detection and quantification was 12.473 ng·mL^(-1) and 24.945 ng·mL^(-1),respectively.The average recovery was 110%,and the RSD was 6.0%(n=9).Conclusion:The method is sensitive and specific,which can be used for the quantification of genotoxic impurity of genotoxic impurity pivaloyl chloride in Cefalexin API.

关 键 词：顶空气相色谱-质谱 头孢氨苄 特戊酰氯 基因毒性杂质 

分 类 号：O657.63[理学—分析化学] TQ460.72[理学—化学]