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With a highly automated approach, Creative Bioarray is providing highly cost-efficient hepatocyte stability assay as one of our in vitro metabolism services and delivers consistent and high quality data.
Drug detoxification and drug metabolism are mostly carried out in the liver. About three-quarters of the drugs cleared via metabolism are metabolized and cleared by hepatic cytochrome P450 (CYP)-mediated metabolism1. Hepatocytes contain the full range of both phase I and phase II hepatic drug metabolizing enzymes thus can serve as a perfect model to determine the in vitro clearance of a compound.
Primary human hepatocytes are considered the Gold Standard for metabolism studies since they contain all the hepatic enzymes, transporters, and co-factors needed for drug metabolism. Hepatocytes can be used in metabolic stability assays, drug efflux and uptake studies, metabolite identification, CYP induction/inhibition studies, etc.
In this assay, hepatocytes are incubated with the test article at 37 °C for different time periods. Samples are removed at each indicated time point during incubation and the reaction is terminated with stop solution. The samples are then centrifuged and supernatants are collected for LC-MS/MS analysis. The clearance of the test article is monitored over a time period of 60 minutes (or longer). Drug clearance rate and half life are then calculated using the obtained data.
Figure 1. Hepatocyte stability profile of three compounds2
Test system available
Different species of hepatocytes can be used in this assay to enable an understanding of interspecies differences in drug metabolism. Those species include human, mouse, rat, rabbit, dog, guinea pig, minipig, and other species.
Creative Bioarray’s hepatocyte stability assay can be further extended to metabolite profiling and give out more information about the metabolism of your compound. Liver microsome stability assay and S9 stability assay are also available at Creative Bioarray. To find out more about our services, please feel free to leave a message below, or contact us at email@example.com or 1-631-626-9181. Our well-experienced experts will be more than happy to help.
|1.||Wienkers, Larry C., and Timothy G. Heath. "Predicting in vivo drug interactions from in vitro drug discovery data." Nature reviews Drug discovery 4.10 (2005): 825-833.|
|2.||Hutzler, J. Matthew, et al. "Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes." Drug Metabolism and Disposition 40.2 (2012): 267-275.|