气相色谱法测定恩替卡韦原料药中有机溶剂残留量

Determination of eight kinds of residual organic solvents in entecavir by GC

目的建立毛细管气相色谱法测定抗病毒原料药恩替卡韦中的有机溶剂残留量。方法采用DB-624毛细管色谱柱,FID检测器。载气为N2,流速为2 ml.min-1,进样口温度250℃,检测器温度为250℃。结果甲醇、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、三乙胺、甲苯和苯甲醇的线性范围分别为0.060 18～0.601 8 g.L-1(r=0.997 3)、0.012 02～0.120 2 g.L-1(r=0.996 8)、0.005 78～0.057 8 g.L-1(r=0.997 2)、0.103 48～1.034 8 g.L-1(r=0.997 2)、0.017 06～0.170 6 g.L-1(r=0.996 8)、0.101 26～1.012 6 g.L-1(r=0.995 7)、0.018 06～0.180 6 g.L-1(r=0.998 3)和0.100 74～1.007 4 g.L-1(r=0.999 3);平均回收率(n=9)分别为98.6%(RSD=2.36%)、95.5%(RSD=5.98%)、96.9%(RSD=4.36%)、100.5%(RSD=2.02%)、102.3%(RSD=3.86%)、100.1%(RSD=1.56%)、102.4%(RSD=1.88%)、99.4%(RSD=1.63%)。结论该方法操作简便、准确、灵敏度高、重复性好,适用于恩替卡韦原料药中有机溶剂残留量的测定。

Objective To establish a capillary gas chromatography method for the determination of residual organic solvents in entecavir. Methods The DB-624 capillary column and FID detector were adopted. The carrier gas was nitrogen with flow rate 2 ml · min-1. The ＇injector temperature and the detector temperature were 250℃. Results Under the selected chromatographic conditions, all solvents were separated and the better separation efficiency between internal and degradation of the sample was obtained. The standard curves were linear in the range of 0.060 18 ～ 0.601 8 g ·L - l （ r = O. 997 3 ） for methanol, 0.012 02 ～ 0.120 2 g · L - l （ r = 0. 996 8 ） for meth- ylene chloride, 0. 005 78 ～0. 057 8 g · L-1 （ r = 0.997 2） for N-bexane, 0. 103 48 ～ 1. 034 8 g · L- 1（ r = 0. 997 2） for ethyl acetate, 0. 017 06 ～ 0.170 6 g · L - 1 （ r = 0. 996 8 ） for tetrahydrofuran, 0.101 26 ～ 1. 012 6 g · L - 1 （ r = 0.995 7 ） for triethylamine, 0.018 06 ～ 0. 180 6 g · L - 1 （ r = 0.998 3 ） for toluene and O. 100 74 ～1. 007 4 g · L - 1 （ r = O. 999 3 ） for phenylcarbinol respectively. The average recov eries（ n = 9） were 98.6% （ RSD = 2.36% ） ,95.5% （ RSD = 5.98% ）, 96.9% （ RSD = 4.36% ）, 100.5% （ RSD = 2.02% ）, 102.3% （RSD=3.86%）,100.1%（RSD=1.56%）,102.4%（RSD=l.88%） and99.4%（RSD=l.63%）,respectively. Conclusion The analytical method is simple, accurate and sensitive with good reproducibility. It can be used to determine the residual organic solvents.