药用橡胶塞中易挥发性物质的浸出物研究

Study on the leachables of volatile substances from pharmaceutical rubber stoppers

关键词:  易挥发物  药用橡胶塞  浸出物  特征指标  评价体系

Key words:  volatile compounds  pharmaceutical stoppers  leachables  characteristic indicators  evaluation system

摘要:

目的 建立不同类型药品的胶塞典型易挥发物的浸出物评价体系，并形成有效的相容性试验策略。方法 采用顶空气质联用色谱（HS-GC-MS）法对六个生产厂家的12批胶塞中的易挥发物进行定性和半定量分析，通过顶空气相色谱（HS-GC）技术，建立了水溶液、醇溶液和脂溶性三种类型药物中特征易挥发物的浸出物测定方法。结果 胶塞中鉴定出正己烷、丙酮、甲苯等9种特征指标，9种化合物的色谱分离效果良好，在各自浓度范围内线性关系良好（r≥0.9992）。检测限为3.6～163.7ng·mL-1、211.3～7999.3ng·mL-1和451.2～8822.3ng·mL-1，回收率为82.8%～103.3%，相对标准偏差RSD为0.9%～6.6%（n=9）。12种药品在不同时间点的迁移量的测定结果表明，胶塞中的易挥发物正己烷和甲基环戊烷的迁移最为显著，且在醇溶性和脂溶性药物中，易挥发物的浸出风险普遍高于水溶性药物。结论 系统性地建立了不同类型药品的胶塞典型易挥发物浸出物的评价体系，为药用橡胶塞的质量控制和用药安全提供支持。 关键词 易挥发物;药用橡胶塞; 浸出物; 特征指标; 评价体系

Abstract:

ABSTRACT: OBJECTIVE To systematically establish an evaluation system for the leachables of typical volatile substances from rubber stoppers for different types of drugs and develop effective compatibility testing strategies. METHODS the study used Headspace Gas Chromatography-Mass Spectrometry (HS-GC-MS) to perform qualitative and semi-quantitative analysis of volatile substances in 12 batches of rubber stoppers from six manufacturers. Through Headspace Gas Chromatography (HS-GC) technology, methods for determining leachables in water-soluble, alcohol-soluble, and lipophilic drugs were established. RESULTS the nine characteristic indicators, including n-hexane, acetone, and toluene, were identified. The chromatographic separation of the nine compounds was effective, and the linear relationship within each concentration range was good (r≥0.9992). The detection limits were 3.6～163.7ng·mL-1, 211.3～7999.3ng·mL-1, and 451.2～8822.3ng·mL-1, respectively. The recovery rates were between 82.8% and 103.3%, and the relative standard deviation (RSD) was between 0.9% and 6.6% (n=9). The determination results of the migration amount of 12 kinds of drugs at different time points showed that the migration of volatile substances such as n-hexane and methylcyclopentane from the rubber stoppers is the most significant, and the risk of leaching of volatile substances were generally higher in alcohol-soluble and lipid-soluble drugs than in water-soluble drugs. CONCLUSION This study systematically establishes an evaluation system for typical volatile leachates from rubber stoppers for different types of drugs, providing support for the quality control and medication safety of pharmaceutical rubber stoppers. Keywords：volatile compounds; pharmaceutical stoppers; leachables; characteristic indicators; evaluation system