应用HPLC-FLD法对棓丙酯注射液生产所用塑料组件中6个多环芳烃的提取及迁移研究  

Research on Extraction and Migration of Six Polycyclic Aromatic Hydrocarbons from Plastic Components Used in Production of Propyl Gallate Injections by HPLC-FLD

作　　者：于亮 张雯 李兆明 张琳 颜红 刘林 徐伟娜 刘燕 张岱州 刘葵葵 Yu Liang;Zhang Wen;Li Zhaoming;Zhang Lin;Yan Hong;Liu Lin;Xu Weina;Liu Yan;Zhang Daizhou;Liu Kuikui(Shandong Provincial Key Laboratory of Chemical Drugs,Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China)

机构地区：[1]山东省药学科学院山东省化学药物重点实验室,济南250101

出　　处：《中国药事》2022年第8期934-942,共9页Chinese Pharmaceutical Affairs

摘　　要：目的:按照《化学药品注射剂生产所用的塑料组件系统相容性研究技术指南(试行)》和《化学药品与弹性体密封件相容性研究技术指导原则(试行)》要求,对生产所用塑料组件中可能含有的6个多环芳烃类物质(PAHs)进行模拟提取及安全评估,并应用迁移试验对下游产品棓丙酯注射液中的相关成分进行测定。方法:采用高效液相色谱-荧光检测法(HPLC-FLD法),使用Kromasil 100-5-C(4.6 mm×250 mm,5μm)色谱柱,流动相为乙腈-水(70∶30,v/v),流速1.2 mL·min,柱温35℃,进样量60μL。FLD激发波长(Ex)分别为270 nm(萘)、250 nm(菲、蒽)、238 nm(芘)、286 nm(苯并[α]蒽)、262 nm(苯并[α]芘),FLD发射波长(Em)分别为335 nm(萘)、380 nm(菲、蒽)、390 nm(芘)、397 nm(苯并[α]蒽)、413 nm(苯并[α]芘)。结果:6个PAHs在各自浓度范围内线性关系良好(r≥0.9979);检测限为0.005~0.037 ng;回收率在99.86%~102.16%,RSD<4%(n=9)。密封件的提取试验结果显示,50%乙醇溶液中能检出多个PAHs,而pH 10缓冲液及注射液的高温高压提取液中能检出微量萘。注射液的迁移试验结果显示,棓丙酯注射液只能迁移进入微量萘,迁移量远低于分析评价阈值(AET)。结论:所用HPLC-FLD法简便、准确,专属性强,灵敏度高,可适用于生产所用塑料组件模拟提取液和注射液中6个PAHs的含量测定。Objective: Under the requirements of “Technical Guide for the Compatibility Study of the Plastic Component System Used in Production of Chemical Drug Injections(Trial)” and “Technical Guidelines for the Study of Compatibility Between Chemicals and Elastomer Seals(Trial)”, simulated extraction and safety evaluation of six polycyclic aromatic hydrocarbons that may be contained in the plastic components used in production were carried out. The relevant components in the downstream product of propyl gallate Injections were determined by the migration test. Methods: Kromasil 100-5-C(4.6 mm×250 mm, 5 μm) chromatographic column was used and the high performance liquid chromatography-fluorescence detection method(HPLCFLD) was performed, injection volume was 60 μL and the column temperature was 35°C with acetonitrile-water(70∶30, v/v) as mobile phase at the fl ow rate of 1.2 mL·min. The excitation wavelengths of fl uorescence detector were 270 nm(naphthalene), 250 nm(phenanthrene, anthracene), 238 nm(pyrene), 286 nm(benzo[α] anthracene)and 262 nm(benzo[α] pyrene) respectively, and the emission wavelengths were 335 nm(naphthalene), 380 nm(phenanthrene, anthracene), 390 nm(pyrene), 397 nm(benzo[α] anthracene) and 413 nm(benzo[α] pyrene)respectively. Results: The six PAHs had a good linear relationship within their respective concentration range(r≥0.9979), and the detection limits were in the range of 0.005-0.037 ng. The recoveries were in the range of 99.86%-102.16%. RSDs were no more than 4%(n=9). The extraction test results of seals showed that multiple PAHs could be detected in 50% ethanol solutions, while a trace of naphthalene could be detected in pH10 buf fers and HTHP(high temperature and high pressure) extracts of injection. The result of injection migration test showed that the propyl gallate Injections could be only migrated into trace naphthalene, and the migration amount was far lower than analytical evaluation threshold(AET). Conclusion: The HPLC-FLD method used in the experiment is simple,

关 键 词：多环芳烃 高效液相色谱-荧光检测法 生产所用塑料组件 棓丙酯注射液 模拟提取试验 迁移试验 

分 类 号：R917[医药卫生—药物分析学]