气相色谱火焰光度法检测TBI-166中硫酸二甲酯和硫酸二乙酯残留量

目的：建立创新药物E-10-（4-三氟甲氧基苯基）-2，10-二氢-3-（2-甲氧基-3-吡啶）氨基-2-（反-4-甲氧基环己基）亚胺吩嗪（TBI-166）中硫酸二甲酯和硫酸二乙酯残留量的气相色谱检测方法。方法：采用DB-WAX毛细管色谱柱，柱温为程序升温（起始温度90℃，保持8 min，以6℃·min^-1升温至120℃，保持5 min），氮气作为载气，使用火焰光度检测器（FPD）检测。结果：硫酸二甲酯和硫酸二乙酯质量浓度分别在0.048 9~0.977 2 μg·mL^-1和0.051 0~1.020 0 μg·mL^-1范围内具有良好的线性，相关系数分别为0.997 2和0.998 0，平均回收率分别为100.1%和99.3%，检测限分别为0.049 μg·mL^-1和0.020 μg·mL^-1；2批TBI-166原料药中均未检测出硫酸二甲酯和硫酸二乙酯。结论：该法经方法学验证，适用于检测药物中硫酸二甲酯和硫酸二乙酯的残留。

Objective: To develop a gas chromatography(GC) method for determining dimethyl sulfate and diethyl sulfate residue in E-10-(4-trifluoromethoxyphenyl)-3-(2-methoxy-3-pyridyl) amino-2-(trans-4-methoxycyclohexyl) imino-2, 10-dihydrophenazine(TBI-166). Methods: A DB-WAX capillary column with nitrogen gas as carrier and flame photometric detector(FPD) as detector were applied in this study. The column temperature was programmed to be:90℃ for 8 minutes, then raised to 120℃ at a speed of 6℃ per minute and held for 5 minutes. Results: The result showed that there was a very good linearity in the range of 0.048 9 to 0.977 2 μg·mL^-1 for dimethyl sulfate(r=0.997 2) and 0.051 0 to 1.020 0 μg·mL^-1 for diethyl sulfate(r=0.998 0). The average recoveries for dimethyl sulfate and diethyl sulfate were 100.1% and 99.3%, respectively. The detection limit was 0.049 μg·mL^-1 for dimethyl sulfate and 0.020 μg·mL^-1 for diethyl sulfate. Dimethyl sulphate and diethyl sulfate were not detected in two batches of TBI-166. Conclusion: The method was proved by methodology validation to be suitable for the detection of dimethyl sulphate and diethyl sulphate in innovative drugs.