卤化丁基橡胶塞助剂润滑剂在羧酸类药物中迁移量的测定

Determination of the Migration of Auxiliary Lubricants from Halogenated Butyl Rubber Stoppers to Carboxylic Acid Drugs

以回收率和精密度为评价指标,考察了甲酯化气相色谱法、无衍生化气相色谱法和HPLC-电雾式检测器(CAD)法测定润滑剂在羧酸类药物中迁移情况的可行性。结果显示,相较于甲酯化气相色谱法和无衍生化气相色谱法,HPLC-CAD法具有较高的回收率和精密度。采用HPLC-CAD法检测润滑剂棕榈酸的回收率、精密度和检出限分别为103.5%~107.8%、1.6%和1.01μg/mL;检测润滑剂硬脂酸的回收率、精密度和检出限分别为100.9%~109.3%、1.4%和1.00μg/mL。随后,将HPLC-CAD法用于检测加速放置0和3个月的丙戊酸注射液,未见润滑剂棕榈酸和硬脂酸自卤化丁基橡胶塞向药液迁移。建立的HPLC-CAD法可用于检测卤化丁基橡胶塞中的润滑剂在羧酸类药物中的迁移情况。

Using recovery rate and precision as evaluation indicators,the feasibility of methyl esterification gas chromatography,non-derivatization gas chromatography,and HPLC method with charged aerosol detector(CAD)for determining the migration of lubricants in carboxylic acid drugs was investigated.The results showed that compared with the methyl esterification gas chromatography and the non-derivatization gas chromatography,the HPLC-CAD method had higher recovery rate and precision.The recovery rate,precision,and detection limit of lubricant palmitic acid by the HPLC-CAD method were 103.5%-107.8%,1.6%,and 1.01μg/mL,respectively.Then,the recovery rate,precision,and detection limit of lubricant stearic acid were 100.9%-109.3%,1.4%,and 1.00μg/mL,respectively.The valproic acid injection after accelerated storage for 0 and 3 months was detected by HPLC-CAD method,and no migration of lubricant palmitic acid and stearic acid was found from halogenated butyl rubber stoppers to the solution.The HPLC-CAD method established in this paper can be used to detect the migration of lubricants from halogenated butyl rubber stoppers to carboxylic acid drugs.