Metabolite Generation Service
Creative Animodel is a leading service provider that focuses on developing metabolite generation analysis for the research of our clients. We provide metabolite generation service to help you analyze drug metabolism process and provide samples for structural elucidation, pharmacology testing or to act as authentic standards.
How Are Metabolites Generated?
Although many organs are capable of metabolizing xenobiotics in animals, the liver is universally recognized as the major site of drug metabolism. Therefore, it is common to use hepatic subcellular fractions such as microsomes and S9 fractions for the generation of metabolites. Fig 1 is a scheme for preparation of subcellular fractions.
Figure 1. A scheme for preparation of subcellular fractions.
The utility of intact hepatocytes offers a viable and advantagous alternative for generation of hepatic metabolites. When prepared correctly, these cells have all their subcellular fractions and compartments intact and functioning, do not require cofactors, will provide sequential metabolism of compounds, and are therefore more representative of in vivo metabolism. Additionally, hepatocytes are correctly predictive of interspecies differences in drug metabolism. The most important factors prohibiting the use of hepatocytes are that it is more complicated to isolate intact fresh hepatocytes than subcellular fractions, it is more costly to procure commercial cryopreserved hepatocytes, and there are limitations associated with cell viability during incubation and freezer storage. It has been recommended that the incubation of hepatocyte suspensions should not exceed 4 hours. It was demonstrated that while this period is sufficiently long to determine metabolic stability and to allow generation of the main metabolites of a test compound, it may be too short to allow generation of some minor, particularly phase II, metabolites.
Metabolite Generation Analysis at Creative Animodel
We provide several LC/MS-MS methods that enable routine analysis of metabolites generated. LC/MS-MS is a very powerful tool for metabolite identification. Metabolites generated from in vitro incubations or in vivo studies can be detected with relative ease. The metabolism information can be conveyed to chemists to address specific metabolic liabilities in the next generation of compounds. It can also be used to facilitate assessment of the exposure to metabolites in humans versus those generated in preclinical studies (usually rat and dog) as recommended by the Metabolites in Safety Testing (MIST) guidance.
• Our metabolite generation system has commercial availability, and the use of subcellular fractions is relatively easy to prepare and store.
• Our LC/MS-MS method is very sensitive, and allows detection of drug candidates and metabolites at subnanomolar concentrations.
• We can provide metabolite generation analysis which is flexible and adaptable to high throughput screening.
Creative Animodel has focused on metabolite generation analysis for many years. Our investigator can quickly determine species differences in metabolite generation that may unravel species differences in rates of clearance and assist in the selection of animal species most relevant to the human. Our in-house expertise and experience can offer the efficient and accurate results to support the continuous study on drug metabolism process. If you have any question, please do not hesitate to contact us. We promise that our professional experts will try their best to satisfy your needs.