Abstract:
:For quantitative in vitro-in vivo extrapolation (QIVIVE) of metabolism for the purposes of toxicokinetics prediction, a precise and robust analytical technique for identifying and measuring a chemical and its metabolites is an absolute prerequisite. Currently, high-resolution mass spectrometry (HR-MS) is a tool of choice for a majority of organic relatively lipophilic molecules, linked with a LC separation tool and simultaneous UV-detection. However, additional techniques such as gas chromatography, radiometric measurements and NMR, are required to cover the whole spectrum of chemical structures. To accumulate enough reliable and robust data for the validation of QIVIVE, there are some partially opposing needs: Detailed delineation of the in vitro test system to produce a reliable toxicokinetic measure for a studied chemical, and a throughput capacity of the in vitro set-up and the analytical tool as high as possible. We discuss current analytical challenges for the identification and quantification of chemicals and their metabolites, both stable and reactive, focusing especially on LC-MS techniques, but simultaneously attempting to pinpoint factors associated with sample preparation, testing conditions and strengths and weaknesses of a particular technique available for a particular task.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Tolonen A,Pelkonen Odoi
10.1016/j.tox.2013.08.010subject
Has Abstractpub_date
2015-06-05 00:00:00pages
20-9eissn
0300-483Xissn
1879-3185pii
S0300-483X(13)00229-1journal_volume
332pub_type
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