顶空气相色谱法测定塞来昔布中硫酸二乙酯基因毒性杂质  

Determination of the diethyl sulphate genotoxic impurity in celecoxib by headspace gas chromatography

作　　者：汪生[1] 倪悦泠 陆宇婷 宋敏[1] 杭太俊[1] WANG Sheng;NI Yue-ling;LU Yu-ting;SONG Min;HANG Tai-jun(Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药物分析系,南京210009

出　　处：《中国新药杂志》2018年第20期2437-2441,共5页Chinese Journal of New Drugs

摘　　要：目的:建立塞来昔布中硫酸二乙酯基因毒性杂质的气相色谱测定方法。方法:采用DB 624毛细管色谱柱(30 m×0. 53 mm,3μm)分离,氮气为载气,碘化钠衍生-顶空进样,甲磺酸异丙酯使用内标法,电子捕获检测器测定塞来昔布中硫酸二乙酯的含量。结果:硫酸二乙酯在40~200 ng·m L-1浓度范围内线性关系良好;平均回收率为90. 37%,RSD为5. 38%;最低检测限为20 ng·m L-1,最低定量限为40 ng·m L-1。在3批塞来昔布供试品中均未检出硫酸二乙酯杂质。结论:建立的硫酸二乙酯基因毒性杂质检测方法专属性好、灵敏度高,适用于塞来昔布及其合成中间体中硫酸二乙酯的测定。Objective： A gas chromatography（ GC） method was developed for the determination of the diethyl sulphate genotoxic impurity in celecoxib. Methods： The separation was performed by using a DB 624（ 30 m × 0. 53 mm,3 μm） capillary column with nitrogen as carrier gas,headspace injection with sodium iodine derivatization and isopropyl methanesulfonate was selected as the internal reference. Electron capture detection was conducted to determinate the content of diethyl sulphate in celecoxib. Results： The observed data showed that satisfactory linearity was obtained in the range of 40 ~ 200 ng·m L-1（ r = 0. 999 3）. The average recovery was90. 37%（ RSD = 5. 38%） and the limit of detection and quantification were 20 and 40 ng·m L-1,respectively.Diethyl sulphate was not detected in the three batches of celecoxib samples. Conclusion： The method was validated to be accurate and specific,and suitable for the determination of the diethyl sulphate genotoxic impurity in celecoxib and related intermediates.

关 键 词：塞来昔布 基因毒性杂质 硫酸二乙酯 衍生化 气相色谱法 

分 类 号：R917[医药卫生—药物分析学]