全降解冠脉雷帕霉素洗脱支架系统有机溶剂残留分析

目的采用顶空进样-气相色谱-质谱联用法(headspace sampling-gas chromatography-mass spectrometry,HS-GC-MS)测试全降解冠脉雷帕霉素洗脱支架系统有机溶剂残留的情况,最终建立顶空进样-气相色谱-氢火焰离子化检测器(headspace sampling-gas chromatography-flame ionization detector,HS-GC-FID)定量测定丙酮残留量的检测方法。方法采用HS-GC-MS,全扫描模式对全降解支架系统中的含药支架、球囊、输送系统、支架原料及裸支架5种被测对象进行残留有机溶剂的定性分析,并采用HS-GC-FID对其中残留较多的丙酮进行了定量分析。结果 5种被测对象中均有多种有机溶剂残留,主要为芳香烃类(甲苯)、酮类(丙酮)、卤化烃类(二氯甲烷、三氯甲烷)、醇类(乙醇等)、酯类(乙酸乙酯等)。丙酮在9.0~44.8μg/m L浓度范围内线性良好,相关系数为0.9995,平均加样回收率为100.3%(n=6,RSD=1.2%),精密度为2.0%(n=5)。结论新产品注册检测含药支架有机溶剂残留的同时,建议考察支架原料、裸支架的有机溶剂残留。建立的定量检测方法简便、快速、准确,可用于全降解支架系统中残留有机溶剂的检测与质量控制。

Analysis of residual organic solvents in biodegradable coronary rapamycin-eluting stents

Objective To measure the residual organic solvents in biodegradable coronary rapamycin-eluting stents using HS-GC-MS and to establish an HS-GC-FID method for the determination of residual acetone in biodegradable coronary rapamycin-eluting stents. Methods A full scan mode of HS-GC-MS was used to analyze the residual organic solvents in the rapamycin-eluting stent,the balloon,the delivery system,raw materials and the bare stent, respectively, and the acetone content in the rapamycin-eluting stent was determined using HS-GC-FID. Results Certain organic solvents were observed, including aromatic hydrocarbon ( toluene),ketone( acetone),halogenated hydrocarbons (methylene chloride and chloroform),alcohols( ethanol, etc. )and esters(ethyl acetate,etc. ). The linear range of acetone was 9. 0 to 44. 8 μg / mL ( r = 0. 9995 ). The average recovery rate was 100. 3%( n = 6,RSD = 1. 2%) and the precision was 2. 0%(n = 5). Conclusions The residual organic solvents in rapamycin-eluting stents,the raw materials and the bare stents should be investigated during the registration evaluation of the biodegradable coronary rapamycin-eluting stents. The quantitative analysis is rapid,accurate and convenient. It is suitable for the determination of the residual organic solvents in biodegradable coronary rapamycin-eluting stents.