恩曲他滨原料药挥发性杂质的研究

GC Determination of Residual Solvents and Impurity of Menthol in the Drug Substance of Emtricitabine

目的建立恩曲他滨原料药中挥发性杂质,包括9种残留溶剂和工艺杂质-薄荷醇限度检查的气相色谱测定方法。方法残留溶剂检查以顶空气相色谱法,氢火焰离子检测器,色谱柱为石英毛细管色谱柱:DB-1(60m×0.32mm×1.00μm),外标法定量;薄荷醇的检测以直接进样气相色谱法,氢火焰离子检测器,色谱柱为石英毛细管色谱柱:DB-1(60m×0.32mm×1.00μm),内标法定量(以乙酸乙酯为内标)。结果 9种溶剂在对照溶液浓度的20%～150%的范围内,峰面积与浓度线性关系良好,9种溶剂的平均加样回收率均在80%以上;薄荷醇在25.0～187.5μg/ml浓度范围内呈良好的线性关系,平均加样回收率为103.2%(RSD=1.67%)。结论 两种气相色谱方法简单、准确、可靠,可用于恩曲他滨原料药残留溶剂和薄荷醇杂质的限度控制。

Objective To establish GC method for the determination of residual organic solvents and menthol in Emtricitabine. Methods The determination of residual solvents was carried out by headspace gas chromatography equipped with a DB - 1 capillary col- umn（60m x0.32mm x 1.00txm） and FID detector. The quantification of residual solvents was calculated by external standard method; The determination of menthol was carried out by direct injection gas chromatography equipped with a DB - 1 capillary column （60m x 0.32mm x 1.00p, m） and FID detector. The quantification of residual solvents was calculated by internal standard method using ethyl ace- tate as the internal standard substance. Results It indicates that the linear correlation of each solvent was fine in the specified range of 20% - 150% of the target concentration. The average recoveries were all over 80%. The linear range of menthol was 25.0 - 187.5μg/ml and the average recovery rate was 103.2% （ RSD = 1.67% ）. Conclusion The two methods are simple, accurate and reliable and can be used h^r lhe quality control of residual solvents and menthol in Emtricitabine.