顶空毛细管气相色谱法测定来曲唑原料药中有机溶剂残留量

目的:建立顶空毛细管气相色谱法测定来曲唑原料药中的三氯甲烷、乙醇、丙酮、乙酸乙酯、N,N-二甲基甲酰胺(DMF)及异丙醇的残留量。方法:以HP-5毛细管柱为色谱柱、二甲基亚砜为溶剂,选择顶空进样法分别测定来曲唑中间品中的三氯甲烷、乙醇、丙酮、乙酸乙酯残留量及来曲唑成品中的DMF和异丙醇残留量。其中,三氯甲烷选用电子捕获检测器,其余有机溶剂选用氢火焰离子化检测器。结果:6种有机溶剂实现基线分离,三氯甲烷、乙醇、丙酮、乙酸乙酯、DMF、异丙醇的线性范围分别为1.028～10.28mg·L-(1r=0.9999)、94.68～946.8mg·L-(1r=0.9997)、94.64～946.4mg·L-(1r=0.9997)、110.64～1106.4mg·L-1(r=0.9997)、15.12～151.2mg·L-(1r=0.9996)、116.48～1164.8mg·L-(1r=0.9995);方法平均回收率为97%～102%;最低检出浓度为20～90μg·L-1;3批中间体和成品样品中均未检出6种有机溶剂,符合《中国药典》要求。结论:该方法简便灵敏,结果准确可靠,能较好地进行来曲唑原料药中有机溶剂残留量的检测。

Determination of Residual Organic Solvents in Letrozole by Headspace Capillary Gas Chromatography

OBJECTIVE： To establish headspace capillary gas chromatography for the content determination of residual solvents in letrozole, such as chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol. METHODS： Dissolved in dimethyl sulfoxide, chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol in letrozole were determined by headspace gas chromatography with HP-5 capillary gas chromatography. ECD was applied for chloroform, while FID was applied for the other residual solvents. RESULTS： The liner ranges of chloroform, ethanol, acetone, ethyl acetate, DMF and isopropanol were 1.028～10.28 mg·L-1（r=0.999 9）, 94.68～946.8 mg·L-1 （r=0.999 7）, 94.64～946.4 mg·L-1（r=0.999 7）, 110.64～1 106.4 mg·L-1（r=0.999 7）, 15.12～151.2 mg·L-1（r=0.999 6）, 116.48～1 164.8 mg·L-1（r=0.999 5）, respectively. The average recoveries of the residual organic solvents ranged from 97% to 102%. The detection limits were 20～90 μg·L-1. The residual levels of the six organic solvents in three batches of samples were all up to the standard stipulated in Chinese Pharmacopeia. CONCLUSIONS： The method is simple, sensitive, accurate and reliable for the content determination of residual organic solvents in letrozole.