液质联用法测定体外循环管道中增塑剂DINCH在血液中的溶出量

目的:建立测定增塑剂环己烷-1,2-二甲酸二异壬酯(DINCH)的测定方法,并测定一次性使用体外循环管道中DINCH在血液中的溶出量,为该产品的安全性评价提供依据。方法:采用乙酸乙酯萃取血液样品中的DINCH,并用液质联用方法(LC-MS/MS)测定一次性体外循环管道中DINCH的溶出量。结果: LC-MS/MS方法测定DINC质量浓度在1.34~53.40 μg·mL^-1范围内线性关系良好(r=0.999 5),灵敏度为0.134 ng,仪器精密度RSD < 5%,液相萃取的回收率为82.11%,用该方法测定一次性体外循环管道在模拟临床使用极限条件下DINCH在血液中的溶出量为2.89 mg·套^-1。结论:本法经方法学验证,可以用于测定DINCH在血液中的溶出量。

Objective:To develop a method for determination of released plasticizer di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH) from disposable extracorporeal circulation tube in blood,so as to evaluate the safety of this product.Methods: Ethyl acetate was used to extract DINCH from blood,and the quantification was achieved by LC-MS/MS.Results: The data on the methodology study of LC-MS/MS showed a good linear relationship of DINCH mass concentration which ranged in 1.34 -53.40 μg·mL^-1 (r=0.999 5).The method sensitivity was 0.134 ng,with an instrumental precision RSD < 5%,and the liquid-phase extraction recovery rate was 82.1%.The amount of DINCH released into blood from this disposable extracorporeal circulation tube was 2.89 mg per set under the maximum clinical conditions.Conclusion: The established method presented high accuracy,good reliability and stability for the determination of DINCH in blood.

[1] XIN FX(辛凤鲜),XUE YY(薛云燕),MA C(马才).Determinated total amount of DEHP released from disposable extracorporeal circulation tube(体外循环管道中DEHP溶出量的测定)[J].China Med Dev Inf(中国医疗器械信息),2011,17(6):36
[2] LIU X(刘曦),YU JJ(于晶晶),LI S(李燊),et al.HPLC method to determine DEHP released into blood from a disposable extracorporeal circulation tube(高效液相色谱法测定一次性体外循环管道中邻苯二甲酸二(2-乙基)己基酯在全血中的溶出量)[J].J Biomed Eng(生物医学工程学杂志),2013,30(4):756
[3] WELLE F,WOLZ G,FRANZ R.Migration of plasticizers from PVC tubes into enteral feeding solutions[J].Pharm Int,2005,3:17
[4] LUO HY,SUN GY,SHI YP,et al.Evaluation of the di(2-ethylhexyl)phthalate released from polyvinyl chloride medical devices that contact blood[J].Springer Plus,2014,3:58
[5] National Industrial Chemicals Notification and Assessment Scheme (NICNAS).Full Public Report:1,2-Cyclohexanedicarboxylic Acid,1,2-Diisononyl Ester ('Hexamoll DINCH'),File No:STD/1259[R].2008
[6] European Commission Health and Consumer Protection Directorate-General.Opinion on the Safety of Medical Devices Containing DEHP Plasticized PVC or Other Plasticizers on Neonates and Other Groups Possibly at Risk[R].2008
[7] OTTER R,GOTH H.Hexamoll Dinch—Our Response to the Plasticizer Challenge[R].Presentation at the Conference Plasticizer.2004
[8] Scientific Committee for Toxicity,Ecotoxicity and the Environment (CSTEE).Opinion on the Results of a Second Risk Assessment of Bis(2-ethylhexyl)phthalate (DEHP) Human Health Part[R].European Commission,C7/GF/csteeop/DEHP/080104 D (04).2004
[9] European Food Safety Authority (EFSA).Opinion of the Scientific Panel on Food Additives,Flavourings,Processing Aids and Materials in Contact with Food (AFC) on a Request Related to a 12th List of substances for food contact materials[R].2006
[10] ANDREÉS,CLAUDIA P,JURGEN A,et al.Quantification of biomarkers of environmental exposure to di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) in urine via HPLC-MS/MS[J].J Chromatogr B,2012,895/896:123
[11] SANDRA B-B,MAURUS B,SUSANNE P,et al.Plasticizers in PVC toys and childcare products:What succeeds the phthalates? Market survey 2007[J].Chromatographia,2008,68(3/4):227
[12] NAGORKA R,CONRAD A,SCHELLER C,ET AL.Diisononyl 1,2-cyclohexanedicarboxylic acid (DINCH) and di(2-ethylhexyl) terephthalate (DEHT) in indoor dust samples:Concentration and analytical problems[J].Int J Hyg Environ Health,2011,214(1):26
[13] DING YM(丁逸梅),LU CX(陆春晓),CUI P(崔萍),et al.Study on the determination of the non-phthalate plasticizer DINCH by GC-MS method and its migration to injections[非邻苯二甲酸酯增塑剂DINCH的GC-MS测定方法的建立及在4种注射剂中的迁移研究][J].Chin J Pham Anal(药物分析杂志),2013,33(10):1731