GC-MS对多西他赛原料药中DMAP和DCC的残留检测

Residue detection of DMAP and DCC in docetaxel by GC-MS

目的采用GC-MS技术对多西他赛原料药中催化剂4-二甲氨基吡啶(DMAP)和脱水剂二环己基碳二亚胺(DCC)进行残留检测。方法色谱柱为安捷伦的DB-5msUI(30m×0.25mm,0.25μm)超高惰性毛细管气相色谱柱;采用程序升温方式,载气为高纯氦气,流速1.5ml/min;进样量为1μl。质谱采用EI源,选择离子监测模式:DMAP的定量离子为121,DCC的定量离子为163,内标龙脑的定量离子为95。多西他赛原料药采用甲醇超声提取。结果 DMAP和DCC的线性关系良好(r>0.999 2),其定量限分别为50.90和10.21ng/ml,日内、日间精密度RSD均小于5.0%,回收率大于90%,符合方法学要求。3批样品中均未检测到DMAP和DCC的残留。结论该方法灵敏度高,专属性好,可用于多西他赛原料药中微量杂质的残留检测。

Objective To establish a GC-MS method for residue detection of 4-Dimethylaminopyridine（DMAP）and Dicyclohexyl Carbodiimide（DCC）in docetaxel.Methods The separation was performed on an Agilent DB-5 msUI capillary column（30 m×0.25 mm,0.25μm）with programmed temperature.The carrier gas was high purity helium,the flow rate was1.5 ml/min and the injection volume was 1μl.Electron impact ion source（EI）and selection monitoring mode（SIM）were applied for quantitative analysis.The quantitative ion of DMAP,DCC and internal standard（IS）was 121,163 and 95 respectively.Docetaxel was ultrasonically extracted with methanol.Results The calibration of DMAP and DCC showed good linear relationship（r0.999 2）,the limits of quantification（LOQ）were 50.90 ng/ml and 10.21 ng/ml separately.Intra-day and interday precision were all less than 5%and recoveries were more than 90%,which conformed with the requirement of methodology validation.No residues of DMAP and DCC were detected in three batches of samples.Conclusion The method was sensitive and selective which can be used for the detection of trace impurities in docetaxel.