毛细管气相色谱法同时检测丙酸氯倍他索原料药中4种有机溶剂残留量

目的:建立丙酸氯倍他索原料药中4种有机溶剂(甲醇、乙醇、N,N-二甲基甲酰胺、二甲亚砜)残留量的检测方法。方法:采用毛细管气相色谱法。色谱柱为HP-INNOWAX石英毛细管柱;溶剂为1,6-二氧六环;程序升温,初始温度60℃,保持5min,并以30℃·min-1速率升温至160℃,保持5min;载气为高纯氮气,流速为1.0mL·min-1;氢火焰离子化检测器温度为250℃;进样口温度为160℃;进样方式为分流进样,分流比为5.0∶1;燃气为氢气,30mL·min-1;助燃气为空气,450mL·min-1;尾吹气为氮气,25mL·min-1;进样量为1μL。在同一条件下检测5批样品中4种溶剂残留量。结果:甲醇、乙醇、N,N-二甲基甲酰胺、二甲亚砜均能达到完全分离,检测浓度线性范围均为0.02～1.0g·L-1(r=1.000);平均回收率为97.6%～102.5%,RSD小于2.88%;最低定量限分别为0.60、0.98、0.38、0.85μg·mL-1;5批样品中有1批检测出甲醇,2批中检测出乙醇,其余均未检测出有机溶剂。结论:该方法灵敏、准确,可同时检测丙酸氯倍他索原料药中4种残留有机溶剂。

Simultaneous Determination of 4 Kinds of Residual Organic Solvents in Clobetasol Propionate by Capillary Gas Chromatography

OBJECTIVE： To establish the method for the content determination of 4 kinds of residual organic solvents （metha- nol, ethanol, N, N-dimethylformamide, dimethylsulfoxide） in clobetasol propionate. METHODS： The residual solvents in beclo- metasone dipropionate were separated on HP-INNOWAX capillary column. 1,6-dioxane was used as solvent. The carried gas was nitrogen at flow rate of 1.0 mL-min-1. The programmed column temperature was set as follows： maintained at 60 ℃ for 5 min and raised to 160 ℃ at the rate of 30 ℃.min-1 followed by holding for 5 min. The injector temperature and FID detector temperature were controlled at 160 ℃ and 250 ℃, respectively. The splitting-ratio was 5.0 ： 1. Hydrogen was use as fuel gas at flow rate of 30 mL.min-1 with air as combustion-supporting gas at flow rate of 450 mL.min-1. The makeup gas was nitrogen at flow rate of 25 mL.min-1. The injection volume was 1 μL. The contents of 4 kinds of residual solvents in 5 batches of samples were determined under same condition. RESULTS： Methanol, ethanol, N,N-dimethylformamide, dimethylsulfoxide in clobetasol propionate were completely separated. The linear ranges were 0.02-1.0 g. L-1 （r=1.000）. Average recovery rates were 97.6%- 102.5% （RSD〈 2.88 % ）. The minimum quantitative concentrations were 0.60 μg. mL- 1, 0.98 μg- mL- t, 0.38 μg. mL- 1, 0.85 μg- mL -1, respectively. Methanol was found in 1 batch of sample and ethanol was found in 2 batches of samples. No organic solvent was found in other batches of samples. CONCLUSIONS： The established method is proved to be accurate and sensitive. It can be used for simultaneous determination of 4 kinds of residual organic solvents in clobetasol dipropionate.