顶空气相色谱法测定利福平中残留溶剂

Determination of residual solvents in rifampicin by headspace gas chromatography

目的利福平原料中残留溶剂的检测方法。方法气相色谱顶空进样法，DB-FFAP毛细管柱（30m×0．32mm×0．25μm），柱温采用程序升温，初始温度为40℃保持5min，然后以15℃／min的升温速率升至220℃保持5min，进样口温度为250℃，FID检测器温度为280℃，分流比为10：1。结果残留溶剂各峰分离度良好，丙酮、乙酸乙酯、乙酸丁酯、正丁醇、ⅣⅣ．二甲基甲酰胺顶空进样检测的色谱峰面积与浓度线性关系良好，线性范围分别为0．1002-1001．7μg／mL（r=1．0000，n=7），0．0997-997．2μg／mL（r=1．0000，n=7），0．0997~996．7μg／mL（r=1．0000，n=7），0．5003-5002．7μg／mL（r=1．0000，n=7），3．5247-352．47μg／mL（r=0．9997，n=7）；最低检测限分别为0．2497、3．974、99．32、0．4533和3．5247μg／mL，3种浓度的平均加样回收率为（n=3）97．0％～103．3％（RSD=0．18％～5．18％），重复性RSD=0．34％～2．79％（n=3）。结论该方法选择性强，灵敏度高，重复性好，可以作为利福平中残留溶剂的质控方法。

Objective To establish a method for the content determination of the residual organic solvents in rifampicin. Methods Headspace GC was adopted. The determination were separated on DB- FFAP（30m×0.32mm×0.25μm） capillary column using temperature programming： the initial temperature was kept at 40℃ for 5 minutes, then the temperature was raised to 220℃ at the rate of 15℃/min and kept for 5 minutes. FID was used as detector with a temperature of 280℃, inlet temperature was 250℃, and the split ratio was 10：1. Results All the peaks were completely separated. The method had good linear relationship with the ranges of 0.1002-1001.7 μg/mL for acetone（r=1.0000, n=7）, 0.0997-997.2pg/mL for ethyl acetate（r=1.0000, n=7）, 0.0997-996.7μg/mL for butyl acetate（r=1.0000, n=7）, 0.5003-5002.7μg/mL for n-butanol（r=1.0000, n=7） and 3.5247-352.47μg/mL for DMF（r=0.9997, n=7）. The detection limits of them were 0.2497ng/mL, 3.974ng/mL, 99.32ng/mL, 0.4533μg/mL and 3.5247μg/mL, respectively. The average recoveries were in the range of 97.0%-103.3% with RSD of 0.18%-5.18%. The range of repeatability RSD was 0.34%-2.79%（n=3）. Conclusion The method is selective, sensitive and repetitive, and can be used to control the residual organic solvents in rifampicin.