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Analytical Strategy to Asses the Safety of Extractables and Leachables of Pharma Packaging
William van Dongen et al.
TNO Quality of Life Utrechtsweg 48, P.O. Box 360, NL-3700 AJ Zeist, The Netherlands Tel: +31 30
694 4542 Fax: +31 30 694 4894 |
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Biography
William D. van Dongen; studied
analytical chemistry at the University of Amsterdam in the Netherlands. In
addition he hold a PhD in peptide/protein mass spectrometry. He worked for
more than ten years as Study Director and R&D manager in the pharmaceutical
industry.
Company Profile
TNO is a knowledge organization
for companies, government bodies and public organizations. The daily work of
some 5,000 employees is to develop and apply knowledge. TNO provide contract
research and specialist consultancy as well as grant licences for patents
and specialist software.
TNO Pharma offers, within its
drug development services, a broad portfolio with regard to testing and
legislation of pharmaceutical packaging. TNO Pharma offers Lead Selection,
Pharmacology, Kinetics & Metabolism, Toxicology, Analytical Services,
Biotechnology, Drug Delivery Testing, Clinical Services and Regulatory
Services. TNO Pharma is located in Zeist which in the centre of the Netherlands.
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Abstract A
cost-effective analytical strategy is being developed aiming to assign
extractables and leachables with structural alerts for genotoxicity that are
present at toxicological relevant concentrations rather than a time
consuming or maybe even impossible peak-by-peak identification and
quantification. For this
purpose the threshold of toxicological concern (TTC) principle is used. The
TTC principle, was defined assuming different threshold values for different
classes of chemicals based on their chemical structures and known toxicity
of chemicals that share similar structural characteristics. The lowest
threshold (0.15 microgram/person/day) is applicable for genotoxic substances
(except for cohort of concern chemicals, e.g. heavy metals, PCBs, dioxins,
furans). Currently TNO is setting up analytical strategies that screen for
specific functional groups (with structural alerts) using mass spectrometric
data. In this presentation the feasibility of the analytical strategy will be demonstrated for aromatic amines, i.e. compounds with a structural alert for genotoxicity. Currently a derivatisation strategy is being developed that specifically assigns aromatic amines in chromatograms of complex mixtures. The results of this study will be presented.
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