盐酸吉西他滨中甲磺酸酯类基因毒性杂质的GC-MS/MS测定  

Simultaneous Determination of Genotoxic Methanesulfonate Impurities in Gemcitabine Hydrochloride by GC-MS/MS

作　　者：姚彤 程青芳 YAO Tong;CHENG Qing-fang(Lianyungang Jari Pharm.Co.,Ltd.,Lianyungang 222000,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]连云港杰瑞药业有限公司,江苏连云港222000 [2]江苏海洋大学药学院,江苏连云港222005

出　　处：《化学试剂》2021年第6期806-810,共5页Chemical Reagents

基　　金：连云港市高新区科技计划项目(ZD201917)。

摘　　要：建立了盐酸吉西他滨中2种甲磺酸酯类基因毒性杂质甲磺酸甲酯和甲磺酸乙酯的气相色谱串联质谱(GC-MS/MS)检测方法。采用VF-WAX ms毛细管色谱柱(30 m×0.25 mm×1.0μm)对这两种甲磺酸酯类化合物进行分离。结果显示,两种化合物在所测浓度范围内线性关系良好;甲磺酸甲酯、甲磺酸乙酯定量限分别为0.0096、0.0087μg/mL,检测限分别为0.0026、0.0029μg/mL。平均加样回收率为97%~100%,RSD≤3%(n=9),且对照品溶液和供试品溶液在25℃放置24 h稳定,RSD≤1.2%。将所建方法用于检测3批盐酸吉西他滨样品,检出了甲磺酸甲酯和甲磺酸乙酯,检出范围分别为0.22~0.40 mg/L和0.12~0.28 mg/L。所建立的分析方法灵敏度高、专属性和准确度好,适用于同时测定盐酸吉西他滨中两种甲磺酸酯类基因毒性杂质,为该药品的质量控制提供参考。A GC-MS/MS method was established for the determination of two genotoxic mesylate impurities in gemcitabine hydrochloride:Methyl methanesulfonate and ethyl methanesulfonate.The separation of methyl methanesulfonate and ethyl methanesulfonate was performed in a VF-WAX ms capillary column(30 m×0.25 mm×0.5μm).The results showed that the linearities of methyl methanesulfonate and ethyl methanesulfonate in the test concentration range were good.The quantification limits of methyl methanesulfonate and ethyl methanesulfonate were 0.0096 and 0.0087μg/mL,respectively.Their detection limits were respectively 0.0026 and 0.0029μg/mL.The average recoveries of methyl methanesulfonate and ethyl methanesulfonate were 97%~100% with RSD(n=9)no more than 3%.The reference solution and test solution were stable at least 24 h at 25℃.The proposed method was applied to detect three gemcitabine hydrochloride samples,and the detection range of methyl methanesulfonate and ethyl methanesulfonate were 0.22~0.40 mg/L and 0.12~0.28 mg/L,respectively.With high sensitivity,good specificity and accuracy,the method established in this work is suitable for the simultaneous determination of methyl methanesulfonate and ethyl methanesulfonate in gemcitabine hydrochloride and provides a reliable method for the quality control of related drugs.

关 键 词：盐酸吉西他滨 基因毒性杂质 甲磺酸酯 气相色谱串联质谱法 

分 类 号：R917[医药卫生—药物分析学]