To compare the metabolic behavior of the test item in different species in in vitro tests.
In vitro tests with liver microsomes, hepatocytes, or enzyme preparations.
The test is generally performed in a system containing liver microsomes, specific systems or hepatocytes. (Tests applying special systems, e.g. supersomes or specific isoenzymes are also possible). Only phase I metabolites will be detected in the samples of a microsomal model, while both phase I and phase II metabolites can be studied in samples originating from a system using hepatocytes. Non-labeled material can be applied for in vitro metabolic profiling tests. Metabolites of samples of non-labeled test substance are analyzed by LC/MS/MS. LC/MS/MS provides additional information concerning the molecular weight and structure of the metabolites produced.
In vitro tests are most suitable for the comparison of the species since microsomal preparations and hepatocytes of many species are available. Eventual species specific metabolites can also be detected.