INVESTIGATION OF IN VITRO METABOLITES OF ETODOLAC IN HUMAN HEPATIC CELL LINE AND CHICKEN LIVER TISSUE USING LC-MS/MS
Keywords:
Keywords, Etodolac, metabolites, hepatic cell lines, chicken liver tissue, LC, LC-MSMSAbstract
Objective: The main objective of this study was to investigate the in vitro metabolic profile of etodolac (ETD) using normal human hepatic cell lines and chicken liver tissue, and to characterize the metabolites obtained using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS).
Methods: In the present study, the metabolic profile of ETD, a well-known non-steroidal anti-inflammatory drug (NSAID), was investigated in normal human hepatic cell lines and chicken liver tissue employing LC-MS/MS technique. The structural details on ETD metabolites were acquired using triple quadrupole mass spectrometer (LCMS-8040, Shimadzu). The metabolites were produced by incubation of ETD with the human hepatic cell lines and chicken liver tissue, at 37 °C for 24 h. The incubated extracts were analyzed with LC-MS/MS and their production spectra were acquired, interpreted and tentative structures were proposed.
Results: Six phase I and phase II metabolites were successfully detected in the proposed study. The metabolic changes observed included-oxidation, N-acetylation, hydrogenation, decarboxylation, methylation and glucuronidation of dehydrogenated ETD. The tentative structures of the metabolites were postulated based on the chemical reactions predicted and the LC-MS/MS data obtained.
Conclusion: The in vitro metabolites of ETD were successfully investigated and characterized in human hepatic cell lines and chicken liver tissue. Also, both the models were found to be equally effective for carrying out the in vitro metabolic study of ETD.
Keywords: Etodolac, Metabolites, Hepatic cell lines, Chicken liver tissue, LC, LC-MS/MS
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