顶空毛细管气相色谱法测定替诺福韦酯原料药中10种残留溶剂  

Determination of 10 residual solvents in tenofovir dipivoxil API by headspace capillary gas chromatography

作　　者：郑银 韩建萍 ZHENG Yin;HAN Jian-ping(API R&D Center, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China)

机构地区：[1]天津药物研究院原料药研发中心

出　　处：《现代药物与临床》2019年第8期2283-2286,共4页Drugs & Clinic

摘　　要：目的建立顶空毛细管气相色谱法测定富马酸替诺福韦二吡呋酯(替诺福韦酯)原料药中甲醇、异丙醇、二氯甲烷、异丙醚、醋酸乙酯、环己烷、乙酸异丙酯、甲苯、N,N-二甲基甲酰胺(DMF)和N-甲基吡咯烷酮10种溶剂残留量。方法 DB-624色谱柱(30 m×0.53 mm×3μm);载气:N2;体积流量:4 mL/min,程序升温:35℃保持10 min,再以20℃/min的速率升温至220℃,保持5 min。进样口温度:230℃,FID检测器,检测器温度:250℃,分流比:10∶1。LOOP:110℃,TR line:120℃,平衡时间:40 min,平衡温度:90℃。结果 10种有机溶剂的分离度均符合要求,线性关系良好(r均大于0.999 0),平均回收率在92.8%~107.0%。结论本方法简便合理,适用于替诺福韦酯原料药中残留溶剂的质量控制,也为其他需要测定沸点和限度均相差较大有机溶剂的原料药提供参考。Objective To establish a headspace capillary gas chromatography method for the determination of residual organic solvents in tenofovir dipyrofuryl fumarate(tenofovir dipivoxil) API, including methanol, isopropanol, dichloromethane, isopropyl ether, ethyl acetate, cyclohexane, isopropyl acetate, toluene, N,N-dimethylformamide(DMF) and N-methyl pyrrolidone. Methods DB-624 chromatographic column(30 m × 0.53 mm× 3 μm) was used, carrier gas was used with N2, and volume flow rate was 4 mL/min. Programmed temperature was 35 ℃ for 10 min, then increased to 220 ℃ as the velocity of 20 ℃/min for 5 min. Sample inlet temperature was 230 ℃, FID detector was used, and detector temperature was set at 250 ℃. Shunt ratio was 10:1, LOOP was110, TR line was 120, equilibrium time was 40 min, and equilibrium temperature: 90 ℃. Results The separation degree of ten organic solvents met the requirements, and the linear relationship was good(r > 0.999 0). The average recovery was between 92.8%and 107.0%. Conclusion The method is simple and reasonable, and can be used for the quality control of residual solvents in tenofovir dipivoxil API. It also provides reference for other API which need to determine boiling point and organic solvents with large difference in boiling point and limit.

关 键 词：替诺福韦酯 残留溶剂 甲醇 异丙醇 二氯甲烷 异丙醚 醋酸乙酯 环己烷 乙酸异丙酯 甲苯 N N-二甲基甲酰胺 N-甲基吡咯烷酮 顶空毛细管气相色谱 

分 类 号：R927.2[医药卫生—药学]