一次性使用输液器中邻苯二甲酸酯增塑剂的迁移及影响因素分析
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摘要
目的研究一次性使用输液器中邻苯二甲酸酯在注射液中的迁移规律。方法将21种注射液根据其性质分成6组,按照临床常用浓度,以每分钟40滴的速度模拟临床输液,收集2 h流出液。按DLLME-GC-MS方法测定流出液中邻苯二甲酸酯的含量。同时考察辅料、接触时间对一次性使用输液器中邻苯二甲酸迁移的影响。结果邻苯二甲酸酯能向其中12种流经一次性使用输液器的注射液迁移。其中在盐酸胺碘酮注射液中,DEHP和DBP的迁移量最大,DBP的迁移量为2.67μg,DEHP的迁移量为104.8μg。聚山梨酯-80、乙醇、丙二醇和苯甲醇等辅料均能促进输液器中的邻苯二甲酸酯的迁移,迁移量随辅料浓度的提高而增大。同时延长接触时间,输液器中邻苯二甲酸的迁移量也随之升高。结论一次性使用输液器中的邻苯二甲酸酯能向与之接触的注射液迁移。迁移量与注射液中的聚山梨酯-80、乙醇、丙二醇和苯甲醇的含量有关,也和接触时间有关。
OBJECTIVE To study the migration of phthalate esters in single use infusion set into injections. METHODS Twenty-one injections were divided into 6 groups based on their properties. All injections were prepared as actual concentration needed by clinic and dripped through single use infusion set for 2 h at the rate of 40 drops per minute. The phthalate esters of the collected solution were detected by DLLME-GC-MS. The effect of excipients and contact time on the migration of phthalate esters were studied as well. RESULTS Phthalate esters were found migrating into 12 injections dripped through single use infusion set. The maximum migration amount of DBP or DEHP was detected in Amiodarone Hydrochloride injection. The amount of DBP in injection was 2.67 μg, while DEHP was 104.8 μg. Excipients such as tween-80, ethanol, propanediol and benzyl alcohol might accelerate the migration of phthalate esters. The migration amount of phthalate esters increased with the increasing of excipients amount. With the prolonging of contact time, the migration amout of phthalate esters would increase as well. CONCLUSION Phthalate esters in single use infusion set may migrate into injections with which the infusion set come into contact. The migration amount is related to the amount of tween-80, ethanol, propanediol and benzyl alcohol in injections, as well as contact time.
OBJECTIVE To study the migration of phthalate esters in single use infusion set into injections. METHODS Twenty-one injections were divided into 6 groups based on their properties. All injections were prepared as actual concentration needed by clinic and dripped through single use infusion set for 2 h at the rate of 40 drops per minute. The phthalate esters of the collected solution were detected by DLLME-GC-MS. The effect of excipients and contact time on the migration of phthalate esters were studied as well. RESULTS Phthalate esters were found migrating into 12 injections dripped through single use infusion set. The maximum migration amount of DBP or DEHP was detected in Amiodarone Hydrochloride injection. The amount of DBP in injection was 2.67 μg, while DEHP was 104.8 μg. Excipients such as tween-80, ethanol, propanediol and benzyl alcohol might accelerate the migration of phthalate esters. The migration amount of phthalate esters increased with the increasing of excipients amount. With the prolonging of contact time, the migration amout of phthalate esters would increase as well. CONCLUSION Phthalate esters in single use infusion set may migrate into injections with which the infusion set come into contact. The migration amount is related to the amount of tween-80, ethanol, propanediol and benzyl alcohol in injections, as well as contact time.
引文
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[2]PASCAL G,SEBASTIEN T,BOUSQUET C,et.al.,Identification and quantification of 14 phthalates and 5non-phthalateplasticizers in PVC medical devices by GC-MS[J].J Chromatogr B,2014,949(6):99-108.
[3]SOBARZO C M,LUSTIG L,PONZIO R,et al.Effects of di(2-ethylhexyl)phthalate on gap and tight junction protein expression in the testis of prepubertal rats[J].Microsc Res Tech,2009,72(1):868-877.
[4]CHAUVIGNéF,MENUET A,LESEN L,et al.Time-and dose related effects of di-(2-ethylhexyl)phthalate and its main metabolites on the function of the rat fetal testis in vitro[J].Environ Health Perspect,2009,117(4):515-521..
[5]ZANG E J,CHEN L,CAO J.Investigation of dissolution of DEHP in packaged infusion sets of paclitaxel injection[J].Chian Pharmacy(中国药房),2008,19(9):698-700.
[6]魏嫣,黄元礼,王丽,等.DEHP和TOTM增塑的PVC一次性输液器与脂肪乳注射液药物相容性研究[J].北京生物医学工程,2016,35(1):41-45.
[7]XU K,LUO H Y,QING Y,SHI Y P.Determination of leachable substances from disposable infusion set during infusion of cefotiam hydrochloride by gas chromatographymass spectrometry[J].J Analyt Sci(分析科学学报),2016,32(2):239-243.
[8]LIU M,WANG X Y.Determination of phthalate ester plasticizers in injections passed through infusion set by dispersive liquid-liquid microextraction[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(7):926-930.