基于气相色谱-质谱法测定塞来昔布中磺酸酯类基因毒性杂质的残留量  

Determination of Sulfonate Genotoxic Impurity Residues in Celecoxib Based on Gas Chromatography-mass Spectrometry Method

作　　者：赵晨阳 刘晓梦 邢亮彬 李亚丽 赵立新 艾连峰 哈婧[2] ZHAO Chenyang;LIU Xiaomeng;XING Liangbin;LI Yali;ZHAO Lixin;AI Lianfeng;HA Jing(Hebei Provincial Drug Review Centre,Shijiazhuang 050091,China;College of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang 050018,China;Shijiazhuang Customs Technology Center,Shijiazhuang 050051,China;College of Public Health,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北省药品审评中心,石家庄050091 [2]河北科技大学化学与制药工程学院,石家庄050018 [3]石家庄海关技术中心,石家庄050051 [4]河北医科大学公共卫生学院,石家庄050017

出　　处：《生物技术进展》2024年第1期85-93,共9页Current Biotechnology

基　　金：河北省市场监督管理局科研计划项目(2021YJ13);河北省卫生厅科研项目(20210700)。

摘　　要：为了建立一种测定塞来昔布原料药及其制剂中塞来昔布磺酸甲酯和塞来昔布磺酸乙酯残留量的气相色谱-质谱(gas chromatography-mass spectrometry,GC-MS)分析方法,采用碘化钠衍生-顶空进样,将两杂质衍生成碘甲烷和碘乙烷,DB624毛细管色谱柱(60 m×0.25 mm,1.4μm)分离,氦气为载气,质谱检测器检测。塞来昔布磺酸甲酯和塞来昔布磺酸乙酯均在10~500 ng·mL^(-1)浓度范围内线性关系良好;回收率在80.87%~106.52%,RSD小于10%;定量限均为10 ng·mL^(-1)。所有塞来昔布样品中均未检测出塞来昔布磺酸甲酯和塞来昔布磺酸乙酯杂质。该方法简便准确,可用于塞来昔布中塞来昔布磺酸甲酯和塞来昔布磺酸乙酯2个磺酸酯类基因毒性杂质的检测。A gas chromatography-mass spectrometry(GC-MS)method was developed for the determination of methyl celecoxib sulfonate and ethyl celecoxib sulfonate residues in celecoxib APIs and their formulations.The two impurities were derivatised into iodomethane and iodoethane by sodium iodide derivatisation with headspace injection,and separated on a DB-624 capillary col⁃umn(60 m×0.25 mm,1.4μm),with helium as the carrier gas and detected by mass spectrometry detector.Both methyl celecox⁃ib sulfonate and ethyl celecoxib sulfonate showed good linearity in the concentration range of 10~500 ng·mL^(-1);the recoveries were in the range of 80.87%~106.52%with the RSDs less than 10%;and the limits of quantification(LOQs)were both 10 ng·mL^(-1).Methyl celecoxib sulfonate and ethyl celecoxib sulfonate impurities were not detected in any of the celecoxib samples.The meth⁃od is simple and accurate,which can be used for the detection of genotoxic impurities of two sulfonate esters,methyl celecoxib sulfonate and ethyl celecoxib sulfonate,in celecoxib.

关 键 词：塞来昔布 塞来昔布磺酸甲酯 塞来昔布磺酸乙酯 基因毒性杂质 气相色谱-质谱法 

分 类 号：Q789[生物学—分子生物学]