Study On The Migration Of Phthalate Esters From PVC Medical Device To Injections By LPME

PVC medical devices containing phthalate ester plasticizers, are widely used in clinic, such as single use blood transfusion device, infusion device. Many researches indicated that phthalate esters would release from PVC medical device and then be injected into patients, which would result in many health problems. The previous researches only focused on one of the phthalate esters, named Di(2-ethyl hexyl) Phthalat (DEHP). The amount of DEHP released from PVC medical device into one or sevreral kinds of injection was detected by general liquid-liquid extraction coupled with GC or HPLC. The present study mainly focused on the migration of six kinds of phthalate esters from PVC injection tubes into 21 kinds of injections with different properties.1. Determination of 6 phthalate esters released from micro syringe pump tube by HF-LPME coupled with gas chromatographyObjective:To develop a method for simultaneous-determination of 6 phthalate esters released from micro syringe pump tube by hollow fiber-based liquid phase microextraction (HF-LPME) coupled with gas chromatography.Methods:After optimizing the main experimental parameters,1.5cm of polypropylene hollow fiber membrane was selected as carrier, and toluene containing benzyl benzoate (internal standard) was selected as extraction solvent. The extraction was carried out with a stirring rate of 500 r-min-1 for 30 min, then 1.0μL of extraction solvent was injected into GC for analysis. The separation was preformed on DB-MS5 capillary (30m×0.25mm×0.25μm) with nitrogen as carrier gas, the oven temperature raised by programming, the injector temperature was 310℃, and the FID detector temperature was set at 300℃.Results:The method exhibited enrichment factor values ranging from 151 to 1189. The limits of detection(LOD) ranged from 0.2 to 7.5μg·L-1(S/N=3). The recoveries were rang from 85.6% to 98.5% with relative standard deviations (RSD) between 4.0% to 11%. DBP and DEHP could be released from micro syringe pump tube into different injection. The maximum migration amounts were 3.24μg and 11.44μg in 8 hours.Conclusion:The method is sensitive, simple and suitable for simultaneous determination of 6 phthalate esters migrated from micro syringe pump tube.2. Determination of phthalate ester plasticizers in injections by DLLME-GC/MS Objective:To develop a method for simultaneous determination of 6 phthalate esters in injections by DLLME-GC/MS.Methods:After optimizing the main experimental parameters, a mixture of extraction solvent (toluene containing benzyl benzoate as internal standard) and surfactant (cetyl-methyl-ammonium bromide) solution was injected into 5.0 ml of sample solution in a glass tube to form an emulsion by the assistance of 1 minutes vortex agitation. After extraction and phase separation by centrifugation under 4000 rmin-1 for 5 minutes, and removal of the aqueous sample, the toluene extract was collected and analyzed by GC/MS. The separation was preformed on HP-MS5 capillary (30 m×0.25 mm×0.25μm) with helium as carrier gas, the oven temperature raised by programming, the injector temperature was 310℃.Results:The method exhibited enrichment factor values ranging from 174 to 280. The limits of detection(LOD) ranged from 0.007 to 0.04ng·L-1 (S/N=3). The recoveries were from 97.8% to 101.2% with relative standard deviations (RSD) of 0.44% to 0.91%. DBP and DEHP were detected in some sample solutions with which PVC medical devices come into contact.Conclusion:The method is sensitive, simple and can be applied for simultaneous determination of 6 phthalate esters in injections.3. Study on the migration of phthalate ester plasticizers in single use infusion set and influence factor analysisObjective:To study the migration of phthalate ester plasticizers in single use infusion set into injections.Methods:21 injections were divided into 6 groups based on their properties. All injections were prepared as per actual concentration needed by clinic and dripped through single use infusion set for 2 hours at the rate of 40 drops per minutes. The phthalate esters of the collected solution were detected by DLLME-GC/MS. The effect of excipients and exposure time on the migration were studied as well.Results:Phthalate ester plasticizers were found being migrated to 12 injections. The maximum migration amount of DBP or DEHP was detected in Amiodarone Hydrochloride Injection. The amount of DBP in injection was 2.67p,g, while DEHP was 104.76μg. Excipients such as tween-80, ethanol, propanediol and benzyl alcohol accelerated the migration of phthalate ester plasticizers. The migration amount of phthalate ester plasticizers increased with the increasing of excipients amount, temperature and exposure time.Conclusion:Phthalate ester plasticizers in single use infusion set may migrate to injections with which the infusion set come into contact. The migration amount is related to excipients including tween-80, ethanol, propanediol and benzyl alcohol, as well as exposure time.