顶空气相色谱法测定盐酸奥布卡因中有机溶剂残留量

Determination of Residual Solvents in Oxybuprocaine Hydrochloride by Head-space Gas Chromatography

目的建立同时测定盐酸奥布卡因原料药中的二氯甲烷、乙酸乙酯、甲醇、乙醇、甲基叔丁基醚、二甲基甲酰胺6种溶剂残留量的顶空气相色谱分析法。方法采用DB-624毛细管柱(30.0 m×0.53 mm,3.00μm),FID检测器,水为溶剂,程序升温,进样口温度200℃,检测器温度200℃,分流进样模式。结果专属性结果表明空白溶剂不会对样品检测造成影响;精密度测定结果表明各溶剂峰面积与保留时间的RSD均不大于10.0%;二氯甲烷、乙酸乙酯、甲醇、乙醇、甲基叔丁基醚、二甲基甲酰胺检测限分别为0.090,0.030,0.903,0.300,0.018,6.666μg/ml,定量限分别为0.300,0.100,3.006,1.000,0.060,22.198μg/ml。甲醇、乙醇、二氯甲烷、甲基叔丁基醚、乙酸乙酯、二甲基甲酰胺分别在0.06~0.45,0.1~0.75,0.012~0.09,0.1~0.75,0.1~0.75,0.03~0.13 mg/ml范围内线性关系良好,平均回收率为100.05%,99.21%,99.65%,99.34%,98.79%,98.99%,RSD均小于5%。结论该方法操作简单,灵敏度及准确度高,可用于对盐酸奥布卡因中6种溶剂残留量同时进行检测。

Objective To establish a head-space gas chromatography method for simultaneous determination of dichloromethane, ethyl acetate, methanol, ethanol, methyl tert-butyl ether and dimethyl formamide in oxybuprocaine hydrochloride active pharmaceutical ingredient. Methods A DB-624 capillary column(30.0 m×0.53 mm, 3.00 μm) with FID detector was adopted, and the temperature was programmed. Water was used as solvent. The injector temperature was 200 ℃, the detector temperature was 200 ℃ and split injection mode was used. Results The specificity results showed that the blank solvent has no effect on the sample detection. The results of precision test show that the RSDs of peak area and retention time of the solvents were not more than 10.0 %. In addition, limits of detection of dichloromethane, ethyl acetate, methanol, ethanol, methyl tert-butyl ether and dimethylformamide were 0.090, 0.030, 0.903, 0.300, 0.018 and 6.666 μg/ml, respectively;and limits of quantitation of the solvents were 0.300, 0.100, 3.006, 1.000, 0.060 and 22.198 μg/ml, respectively. The calibration curves for methanol, ethanol, dichloromethane, methyl tert-butyl ether, ethyl acetate and dimethylformamide were linear in the ranges of 0.06-0.45, 0.1-0.75, 0.012-0.09, 0.1-0.75, 0.1-0.75, 0.03-0.13 mg/ml, respectively. The average recoveries were 100.05 %, 99.21 %, 99.65 %, 99.34 %, 98.79 %, 98.99 %, with RSDs less than 5 %. Conclusion The method is simple, accurate and sensitive. It can be used for the determination of 6 residual solvents in oxybuprocaine hydrochloride.