顶空气相色谱法测定15-羟基硬脂酸聚乙二醇酯中环氧乙烷和二氧六环含量

Determination of ethylene oxide and dioxane in 15-hydroxystearic acid polyethylene glycol ester by headspace gas chromatography

目的:建立顶空气相色谱法测定药用辅料15-羟基硬脂酸聚乙二醇酯中的残留杂质环氧乙烷和二氧六环的含量。为15-羟基硬脂酸聚乙二醇酯的质量控制提供参考和依据。方法:参考国内外药典方法,选用色谱柱DB-5(15 m×0.32 mm, 1μm),以5%苯基-95%甲基聚硅氧烷为固定液,采用程序升温模式:起始温度为35℃,维持5 min,以每分钟5℃的速率升温至180℃,然后以每分钟30℃的速率升温至250℃,维持5 min。进样口温度为150℃,检测器温度为250℃,顶空平衡温度70℃,平衡时间45 min,分流比为10∶1。按标准加入法计算供试品中环氧乙烷和二氧六环的含量。结果:在该色谱条件下,环氧乙烷和二氧六环分别在0.5~4μg·mL^(-1)和5~40μg·mL^(-1)范围内线性关系良好(r≥0.99);平均回收率均为75%(RSD=5%,n=9)。来自三个厂家的五批次样品均未检测出环氧乙烷,其中一批样品未检出二氧六环,另外四批样品中二氧六环含量均小于0.005%,符合限度要求。结论:该方法适用于15-羟基硬脂酸聚乙二醇酯中环氧乙烷和二氧六环含量测定,为15-羟基硬脂酸聚乙二醇酯的质量控制提供了参考与指导。

Objective:A headspace Gas chromatography was established for the determination of residual impurities oxirane and dioxane in 15-hydroxystearic acid polyethylene glycol ester.It provides reference and basis for the quality control of 15-hydroxystearic acid polyethylene glycol ester.Methods:Reference to domestic and foreign pharmacopoeia methods.The chromatographic column DB-5(15 m×0.32 mm,1μm)was selected with 5%phenyl-95%methylpolysiloxane as stationary liquid,and the programmed temperature model was adopted:the initial temperature was 35℃,and maintained for 5 min,at a rate of 5℃per minute to 180℃,and then at a rate of 30℃per minute to 250℃for 5 minutes.The inlet temperature was 150℃,the detector temperature was 250℃,the headspace equilibrium temperature was 70℃,the equilibrium time was 45 min,and the shunt ratio was 10∶1.The contents of oxirane and dioxane in the samples were calculated by standard addition method.Results:Under this chromatographic condition,oxirane and dioxane showed a good linear relationship in the range of 0.5-4 and 5-40μg·mL^(-1) respectively(r≥0.99),and the average recovery was 75%(RSD=5%,n=9).No oxirane was detected in four batches of samples from three manufacturers.In one batch of samples,no dioxane was detected.In the other four batches of samples,the dioxane content was less than 0.005%,which met the requirement of the limit.Conclusion:The method is suitable for the determination of ethylene oxide and dioxane in 15-hydroxystearic acid polyethylene glycol ester,and provides reference and guidance for the quality control of 15-hydroxystearic acid polyethylene glycol ester.