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Identification and quantification by 1H nuclear magnetic resonance spectroscopy of seven plasticizers in PVC medical devices

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Abstract

Medical devices are generally made of polyvinyl chloride plasticized by six authorized plasticizers as alternatives to di-(2-ethylhexyl)-phthalate (DEHP) classified as reprotoxic class 1b. These are acetyl tri-n-butyl citrate (ATBC), di-(2-ethylhexy) adipate (DEHA), di-(2-ethylhexyl) terephthalate (DEHT), di-isononyl cyclohexane-1,2-dicarboxylate (DINCH), di-isononyl phthalate (DINP), and tri-octyl trimellitate (TOTM). The main objective of this study was to propose a new method using 1H NMR spectroscopy to determine and quantify these seven plasticizers in PVC sheets, standard infusion tubings, and commercially available medical devices. Two techniques were compared: dissolution in deuterated tetrahydrofuran and extraction by deuterated chloroform. Plasticizer 1H NMR spectra were very similar in both deuterated solvents; dissolution and extraction provided similar results. The sensitivity of this method enabled us to detect and quantify the presence of minor plasticizers in PVC. In nine commercially available samples, the major plasticizer was identified and quantified by 1H NMR. In six samples, one, two, or three minor plasticizers were identified and also quantified. DEHP was detected in only one tubing. NMR is therefore very convenient for studying plasticizers contained in medical devices. Only small quantities of solvents and sample are required. It is not necessary to dilute samples to enter a quantification range, and it is sufficiently sensitive to detect contaminants.

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Acknowledgments

This study is part of the project “Assessment and Risk Management of Medical Devices in Plasticized Polyvinylchloride (ARMED)” which has received financial support from the French Medicine Agency (ANSM, Agence Nationale de Sécurité du Médicament et des Produits de Santé). The authors wish to thank the collaborators of the ARMED study group in task 1 “Characterization of plasticizers in medical devices”: Lise Bernard, Daniel Bourdeaux, Philip Chennell, Teuta Eljezi, Jérémy Pinguet, Damien Richard, Bruno Pereira Valérie Sautou, and Mouloud Yessaad (University Hospital, Clermont-Ferrand, France); Nathalie Azaroual, Christine Barthelémy, Bertrand Décaudin, Thierry Dine; Frédéric Feutry, Stéphanie Genay, Nicolas Kambia, Marie Lecoeur, Morgane Masse, Pascal Odou, Nicolas Simon, and Claude Vaccher (EA 7365, University of Lille 2, France); Régis Cueff and Emmanuelle Feschet (EA 4676 C-Biosenss, Auvergne University, France); and Colette Breysse (Technology Research Centre 3S Inpack, Aubière).

The 500 MHz NMR facilities were funded by the Région Nord-Pas de Calais (France), the Ministère de la Jeunesse, de l’Education Nationale et de la Recherche (MJENR), and the Fonds Européens de Développement Régional (FEDER).

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Authors and Affiliations

  1. Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000, Lille, France

    Stéphanie Genay, Frédéric Feutry, Morgane Masse, Christine Barthélémy, Pascal Odou, Bertrand Décaudin & Nathalie Azaroual

  2. Clermont Université, Université d’Auvergne, CHU Clermont-Ferrand, EA 4676, C-BIOSENSS, BP 10448, F-63000, Clermont-Ferrand, France

    Valérie Sautou

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  1. Stéphanie Genay
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  2. Frédéric Feutry
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  3. Morgane Masse
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  4. Christine Barthélémy
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  5. Valérie Sautou
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  7. Bertrand Décaudin
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  8. Nathalie Azaroual
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Armed Study Group

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Correspondence to Bertrand Décaudin.

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Genay, S., Feutry, F., Masse, M. et al. Identification and quantification by 1H nuclear magnetic resonance spectroscopy of seven plasticizers in PVC medical devices. Anal Bioanal Chem 409, 1271–1280 (2017). https://doi.org/10.1007/s00216-016-0053-4

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  • DOI: https://doi.org/10.1007/s00216-016-0053-4

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