Residue detection of DMAP and DCC in docetaxel by GC-MS
-
摘要: 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(30 m×0.25 mm,0.25 μm)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1.5 ml/min;进样量为1 μl。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10.21 ng/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。Abstract: 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-5msUI capillary column (30 m×0.25 mm, 0.25 μm) with programmed temperature. The carrier gas was high purity helium, the flow rate was 1.5 ml/min and the injection volume was 1 μl. 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 (r>0.999 2), the limits of quantification (LOQ) were 50.90 ng/ml and 10.21 ng/ml separately. Intra-day and inter-day 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.
-
Key words:
- GC-MS /
- docetaxel /
- DMAP /
- DCC /
- residue detection
-
[1] 徐少杰,袁建勇,周辉,等. 多西他赛合成工艺[J]. 科技导报, 2010, 28(13):82-86. [2] 孟秀敏. 多西他赛联合卡培他滨治疗紫杉醇耐药乳腺癌患者40例[J]. 中国药业, 2013, 22(17):64-65. [3] 黄和,李丕宏,张毅,等. 多西他赛联合奥沙利铂及氟尿嘧啶治疗晚期胃癌临床观察[J]. 浙江医学, 2011, 33(2):183-185. [4] 朱庆华,张国兵. 多西他赛与奈达铂联合治疗晚期非小细胞肺癌的临床疗效观察[J]. 中国现代医生, 2015, 53(20):89-92. [5] 孙继国,周自成,夏玲远. 4-二甲氨基吡啶(DMAP)在医药合成中的应用[J]. 沧州师范学院学报, 2014, 30(1):49-53. [6] WIKIPEDIA. DMAP. Wikipedia website (2016). (2016-09-18).[2018-03-07]. https://en.wikipedia.org/wiki/4-Dimethylaminopyridine. [7] SAVJANI JK, MULAMKATTIL S, VARIYA B, et al. Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents[J]. Eur J Pharmacol, 2017, 801:28-34. [8] 薄采颖,毕良武,王玉民,等. DCC及其在有机合成中的应用[J]. 化工时刊, 2007, 21(10):4-6. [9] 范小振,张小杰,徐宝军. 高效液相色谱法测定烯草酮合成废液中4-二甲氨基吡啶含量[J]. 化学研究与应用, 2015, 27(2):237-239. [10] 刘义国,郝文明. 气相色谱法分析N,N'-二环己基碳二亚胺的纯度[J]. 山东化工, 1998, 27(5):39-40.
计量
- 文章访问数: 3980
- HTML全文浏览量: 708
- PDF下载量: 515
- 被引次数: 0