In vitro Investigation of Metabolic Profiling of a Potent Topoisomerase Inhibitors Fluorescein Hydrazones (FLHs) in RLMs by LC-MS/MS

- Metabolic profiling of two newly reported topoisomerase inhibitors in rat liver microsomes (RLMs).
- Data were acquired in a liquid chromatography (LC) ion trap tandem mass spectrometry.
- Various metabolites were identified and.
- Structures of those identified metabolites were elucidated by MS2 fragmentation pattern

Metabolic profiling of newly reported two topoisomerase inhibitors namely fluorescein hydrazones (FLHs) were studied in rat liver microsomes (RLMs) and the data were acquired in a liquid chromatography (LC) ion trap mass spectrometry. (E)-3',6'-dihydroxy-2-((2-nitrobenzylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (1) was bio-transformed into two mono-hydroxylated, one double hydroxylated and a tetra hydroxylated metabolites, on the other hand, (Z)-3',6'-dihydroxy-2-((2-oxoindolin-3-ylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (2) was bio-transformed into eight possible metabolites by cleavage reduction, hydroxylation, cleavage reduction together with hydroxylated and azo-reduction in RLMs in presence of NADPH-generating system. No metabolites were generated in the absence of either NADPH or microsomes for the compounds (1 and 2), indicating a likely involvement of CYP450 enzymes and the cofactor NADPH in the metabolisms. The structures of those metabolite were elucidated by MS/MS fragmentation study.