恩替卡韦原料药中多种残留溶剂测定方法研究

目的：建立恩替卡韦原料药中残留溶剂甲醇、乙醇、叔丁醇、叔丁基甲基醚、乙酸乙酯、四氢呋喃、正庚烷、甲苯、N，N-二甲基甲酰胺的测定方法。方法：采用气相色谱直接进样法，利用氢火焰离子化检测器、6%氰丙基苯基-94%二甲基硅氧烷毛细管色谱柱，应用程序升温（40℃，保持5 min，以5℃/min的速度升温至90℃，再以10℃/min的速度升温至180℃，保持3 min），进样口温度180℃，检测器温度250℃，载气为N2，以二甲基亚砜为溶剂配制对照品溶液及样品溶液，采用外标法定量。结果：几种残留溶剂在对应于限度的50%～150%浓度范围内有良好的线性关系（r ＝0.9986～0.9999）；平均回收率为90.63%～99.69%， RSD 为0.23%～6.34%。结论：该方法简单、可靠、精确，可用于恩替卡韦原料药残留溶剂的测定。

Determination of Residual Solvents in the API of Entecavir

Objective：To establish a method for the determination of residual solvents of methanol , ethanol , tert-butanol , methyl tert-butyl ether , ethyl acetate , tetrahydrofuran , n-heptane , toluene and N , N-dimethyl formamide in the API of entecavir . Methods： FID detector and 6% cyanopropyl phenyl -94% two methyl siloxane capillary chromatographic column were adopted with capillary gas chromatography method . Standard solution and test solution were introduced by direct injection . The injector temperature was at 180℃and the detector temperature was at 250 ℃. The column temperature was programmed raised （ at 40 ℃ for 5 min , at the speed of 5 ℃/min up to 90 ℃, then at the speed of 10 ℃/min up to 180℃ for 3 min ） . The carrier gas was nitrogen , and the solvent was DMSO . The residual solvents were quantified by external standard method . Results： The correlation coefficients of linearity ranged from 0 . 998 6 to 0 . 999 9 for the organic residual solvents within the concentration of 50% to 150% of relative individual limit specified . The average recovery rate was 90 . 63% ~ 99 . 69%, RSD was 0 . 23%~6 . 34%. Conclusion：This method was simple , reliable and accurate for the quantitative determination of residual solvents , and can be used for the quality control of the API of entecavir .