毛细管气相色谱法测定利伐沙班原料药中4种残留有机溶剂  

Determination of 4 residual organic solvents in rivaroxaban drug substance by capiiiary gas chromatography

作　　者：刁岩忠 吴卫军[2] 常江 曹燕锋 

机构地区：[1]南京优科生物医药集团股份有限公司,南京210009 [2]南京大学医学院附属鼓楼医院药学部,南京210008

出　　处：《中南药学》2017年第5期650-653,共4页Central South Pharmacy

摘　　要：目的建立测定利伐沙班原料药中丙酮、乙醇、甲苯、乙酸残留量的方法。方法采用直接进样毛细管气相色谱法。色谱柱为以硝基对苯二甲酸改性的聚乙二醇(DB-FFAP)为固定液的石英毛细管柱(30 m×0.53 mm,1.0μm);柱温为程序升温:初始温度50℃,保持15 min,以10℃·min-1升至150℃,保持5 min;进样口温度为200℃;检测器为氢火焰离子化检测器(FID),温度为250℃;载气为氮气,流速为5 m L·min-1;分流比为20∶1;进样量为1μL。外标法进行定量,并对分离条件进行研究。结果丙酮、乙醇、甲苯、乙酸的检测进样量线性范围分别为50.53~505.3 ng(r=0.9998)、49.87~498.7 ng(r=0.9998)、8.944~89.44 ng(r=0.9997)、49.76~497.6 ng(r=0.9997);定量限分别为2.51、5.05、4.62、25.70 ng;检测限分别为0.753、1.52、1.39、7.71 ng;精密度、稳定性、重复性试验的RSD均<3%;平均加样回收率分别为99.8%~101.9%、99.7%~102.0%、99.8%~100.5%与100.0%~100.9%RSD均<3%。结论该方法快速、准确、灵敏度高、重复性好,可作为利伐沙班中有机溶剂残留量的测定方法。Objective To determine actone, ethanol, toluene and acetic acid in rivaroxaban drug substance. Methods A capillary gas chromatographic method with directly sampling was used. The chromatographic column was DB-FFAP（30 m×0.53 mm, 1.0 μm） modified capillary column, the column temperature was programmed. The initial temperature was 50 ℃ maintained for 15 min; then rase to 150 ℃ at a rate of 10 ℃·min^-1, and maintained for 5 min. The injector temperature was 200 ℃. The detector was FID at 250 ℃. The carrier gas was nitogen, and the flow rate was 5 m L·min^-1. The split ratio was 20∶1. The injection volume was 1 μL. Results The standard curves were linear at 50.53-505.3 ng（r = 0.9998） for actone, 49.87-498.7 ng（r= 0.9998） for ethanol, 8.944-89.44 ng（r = 0.9997） for toluene, and 49.76-497.6 ng（r = 0.9997） for acetic acid. The average recoveries were 99.8%-101.9%, 99.7%-102.0%, 99.8%-100.5% and 100.0%-100.9%, and the RSDs were all less than 3%. Conclusion The method is rapid, accurate, sensitive, and repeatable, which can be used to detect residual organic solvents in rivaroxaban.

关 键 词：毛细管气相色谱法 利伐沙班 有机溶剂残留量 

分 类 号：R917[医药卫生—药物分析学] R927.11[医药卫生—药学]