Determination of tris(2-ethylhexyl)trimellitate released from PVC tube by LC–MS/MS

Ito, Rie; Miura, Naoko; Iguchi, Hirofumi; Nakamura, Hiroko; Ushiro, Masaru; Wakui, Nobuyuki; Nakahashi, Keisuke; Iwasaki, Yusuke; Saito, Koichi; Suzuki, Tsutomu; Nakazawa, Hiroyuki

doi:10.1016/j.ijpharm.2008.04.020

Cited by 39 publications

(13 citation statements)

References 21 publications

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“…TOTM is released in far smaller amounts than DEHP in the same conditions of use, principally as a result of its higher molecular weight and greater steric hindrance and its lower solubility in water [6, 7, 41]. Bernard et al (2015) [6] showed that only 0.2% of the total initial amount of the TOTM present in the tubing migrated into a simulant (migration tests conducted at 40 °C in a temperature-controlled chamber for 24 h).…”

Section: Discussionmentioning

confidence: 99%

Exposure of hospitalised pregnant women to plasticizers contained in medical devices

et al. 2017

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BackgroundMedical devices (MDs) in polyvinyl chloride (PVC) are not a well-known source of exposure to plasticizers, in particular during pregnancy. Because of its toxicity, the di-(2-ethylhexyl) phthalate (DEHP) has been replaced by other plasticizers such as di (isononyl)-cyclohexane-1,2-dicarboxilic acid (DINCH), tri-octyltrimellitate (TOTM) and di-(isononyl) phthalate (DiNP). Our study aimed to quantify the plasticizers (DEHP and alternative plasticizers) contained in PVC medical devices used for hospitalised pregnant women and to describe which these MDs had been used (type, number, duration of exposure).MethodsThe plasticizers contained in the MDs used for daily care in the Obstetrics Department of a French University Hospital were extracted from PVC (after contact with a chloroform solution), identified and quantified by gas-chromatography-mass-spectrometry analysis. A total of 168 pregnant women hospitalised in the Obstetrics Department with at least one catheter were included in the observational study. The median number of MDs containing plasticizers used and the daily duration of exposure to the MDs were compared in three groups of pregnant women: “Pathology group” (women hospitalised for an obstetric disorder who did not give birth during this hospitalisation; n = 52), “Pathology and delivery group” (hospitalised for an obstetric disorder and who gave birth during this stay; n = 23) and “Delivery group” (admitted for planned or spontaneous delivery without obstetric disorder; n = 93).ResultsDiNP, TOTM and DINCH were the predominant plasticizers contained in the MDs at an amount of 29 to 36 g per 100 g of PVC. Women in the “Pathology group” (preterm labour or other pathology) were exposed to a median number of two MDs containing TOTM and one MD containing DiNP, fewer than those in the “Pathology and delivery group” (p < 0.05). Women in the “Pathology group” had a median exposure of 3.4 h/day to MDs containing DiNP and 8.2 h/day to MDs containing TOTM, longer than those in the “Delivery group” (p < 0.01).ConclusionsOur study shows that the medical management of pregnant women in a hospital setting entails exposure to MDs containing alternative plasticizers (DiNP, TOTM and DINCH).Electronic supplementary materialThe online version of this article (doi:10.1186/s12905-017-0398-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Exposure of hospitalised pregnant women to plasticizers contained in medical devices

et al. 2017

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“…Because of this, transfer tubing, transfusion sets and blood bags have been intensively examined as sources of DEHP [1][2][3][4][5][6][7] and other kinds of polymers have been proposed as packaging material for pharmaceutical formulations. 8,9 The presence and the release of DEHP have been also investigated in extracorporeal circulation circuits such as hemodialyzers 10 and extracorporeal membranes of oxygenation circuits. 11,12 Concerns are related to the potential health hazards that are associated with the release of DEHP from devices made of PVC.…”

Section: Introductionmentioning

confidence: 99%

Migration of phthalate-based plasticizers from PVC and non-PVC containers and medical devices

Veiga¹,

Bohrer²,

Nascimento³

et al. 2012

J. Braz. Chem. Soc.

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A presença de cinco plastificantes derivados de ftalatos em equipamentos para administração intravenosa de soluções e em hemodialisadores (HD), que são feitos tanto de policloreto de vinila (PVC) quanto de outros materiais poliméricos, foi investigada. Destes ftalatos, o único autorizado por agências reguladoras é o di-(2-etilhexil) ftalato (DEHP) em equipamentos de PVC. A determinação foi feita por chromatografia líquida de alta eficiência (HPLC) com detecção UV. Os resultados mostraram que as bolsas para infusão que são feitas tanto de PVC quanto de etil vinil acetato (EVA) contêm apenas DEHP. Entretanto, as mangueiras dos equipos de infusão e dos HD, bem como as fibras capilares dos HD feitas de celulose, contêm não só DEHP, mas também ftalato de dibutila (DBP). Todos os cinco ftalatos investigados foram encontrados nos capilares dos HD feitos de polisulfona. A migração de DEHP para soluções (aminoácidos, glicose e salina) armazenadas em bolsas ocorreu com taxas diferentes para os dois polímeros. Enquanto que para as bolsas de PVC o DEHP foi encontrado em soluções já nos primeiros dias de contato, para as bolsas de EVA a migração iniciou após aproximadamente 6 meses de armazenamento. Como os dispositivos analisados, com exceção das bolsas, contém, além do DHEP, outros ftalatos, o risco posto aos pacientes deve ser motivo de preocupação.The presence of five plasticizer phthalates in bags and sets for intravenous administration and hemodialyzers (HD), which are made of polyvinyl chloride (PVC) and of other polymeric materials, was investigated. Di-(2-ethylhexyl) phthalate (DEHP) in PVC is the only authorized phthalate by regulatory agencies. Phthalate determination was carried out by high resolution liquid chromatograph (HPLC) with UV detection. The results showed that the infusion bags that are made of both PVC and ethylene vinyl acetate (EVA) contained only DEHP. In contrast, the tubing of infusion sets and of HD (as well as the cellulose capillaries of HD) contained not only DEHP but also dibutyl phthalate (DBP). Moreover, all five investigated phthalates were found in HD polysulfone capillaries. Migration of DEHP into the stored solutions (amino acids, glucose and saline) in bags occurred at different rates from one polymer to another. While DEHP from PVC bags was found in solutions within the first days of contact, the migration from EVA bags started only after approximately 6 months of solution storage. Since PVC and non-PVC devices (as well as capillaries of HD sets) contain DEHP and other phthalate-based plasticizers, the extent of the risk that they pose to patients remains a matter of concern.

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“…An alternative to DEHP plasticized PVC is Tri-2-ethylhexyl trimellitate (TOTM) plasticized PVC, which is believed to have lower toxicity (ExxonMobil Biomedical 2001 ;Czuba et al 1996 ), and has been shown to have lower migration rates (Czuba et al 1996 ;Ito et al 2008 ).…”

Section: Materials Of Constructionmentioning

confidence: 99%

Intravenous Admixture Compatibility for Sterile Products: Challenges and Regulatory Guidance

Sharma

Cheung

Dabbara

et al. 2013

Sterile Product Development

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Intravenous (IV) administration of many sterile drug products requires admixture preparation using a diluent, brief storage in an IV container, and dosing through an infusion device. To ensure patient safety and drug effi cacy, regulatory agencies require that the sterile drug product is compatible with the diluents and the infusion devices. Therefore, admixture compatibility and stability studies are key components of the pharmaceutical development process. On the surface these studies may seem straightforward, but in practice they require detailed planning, meticulous execution, and appropriate data analysis. The purpose of this chapter is to discuss various requirements and challenges associated with conducting IV admixture studies and the related regulatory guidance. IntroductionIntravenous (IV) administration of many sterile drug products requires admixture preparation using a diluent prior to administration. A pharmaceutical admixture consists of a drug product mixed with an appropriate diluent in a suitable dosing/ delivery device for the purpose of parenteral infusion to the patient. Regulatory agencies, as a part of registration requirements, have listed specifi c requirements for the demonstration of the compatibility of the drug product with the diluents and with the infusion devices. For example, as per ICH Q8 guideline, the compatibility of the drug product with reconstitution diluents should cover the recommended in-use shelf life, at the recommended storage temperature and at the likely extremes of concentration (ICH 2009 ). Similarly, guidance for industry from the U.S.

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Determination of tris(2-ethylhexyl)trimellitate released from PVC tube by LC–MS/MS

Cited by 39 publications

References 21 publications

Exposure of hospitalised pregnant women to plasticizers contained in medical devices

Exposure of hospitalised pregnant women to plasticizers contained in medical devices

Migration of phthalate-based plasticizers from PVC and non-PVC containers and medical devices

Intravenous Admixture Compatibility for Sterile Products: Challenges and Regulatory Guidance

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