We can perform isolation of targeted metabolite(s) from various in vitro and in vivo matrices followed by unambiguous structural elucidation using NMR. If isolation of metabolites is not feasible from biological matrices, we offer a complimentary approach – biomimetic oxidation.
Metabolite ID (EA412)
Metabolite ID without Structure Elucidation (EA438)
Metabolite ID with Structure Elucidation (EA439)
Screening Metabolite ID without Structure Assignment (EA436)
Screening Metabolite ID with Structure Assignment (EA437)
Glutathione Trapping in Human Liver Microsomes
By adding oxygen donors (like hydrogen peroxide) to metallorganic complexes (synthetic metalloporphines), we can mimic the action of CYP450 and generate milligram quantities of metabolites identical to detected in biological samples. We can then test these metabolites for safety and drug-drug interaction potential to enable comprehensive safety evaluation or send them back to the client for in house evaluation of pharmacological activity."
To identify the types of metabolism assays that need to be conducted we start with a preliminary stability assessment of the NME
• Identification of unique and disproportionate metabolites
• Selection of appropriate pre-clinical tox models
• In vivo metabolites in clinical samples.
• Soft spot identification
Biomimetic Metabolite Generation and Characterization
We can generate high-milligram quantities of Phase I metabolites in vitro for structural confirmation, characterization of unique or abundant metabolites, in vitro characterization of drug-drug interaction potential and preliminary studies.
Determine half-life (t1/2) and intrinsic clearance (CLint) in human and animal liver and intestinal microsomes, S9 fraction, hepatocytes, and extrahepatic subcellular fractions.
Simplified with Exemplary Service
Absorption Systems provides a clear advantage with results you can trust. Research managers are dedicated to your project, acting as your personal Data Concierge™ — delivering projects on time and on budget.
How does Absorption Systems do metabolite ID?
• Generate metabolites in vitro or in vivo
• Utilize high-resolution mass spec coupled with data-dependent acquisition of MS(n) data
• Perform structural elucidation
• Quantify and determine relative abundance of metabolites
• Use MetaSite software to complement the results from LC-MS/MS
• Available: Structure confirmation by NMR and synthesis of metabolites using biomimetic oxidation
EA412 Metabolite ID
EA438 Metabolite ID without Structure Elucidation
EA439 Metabolite ID with Structure Elucidation
EA436 Screening Metabolite ID without Structure Assignment
EA437 Screening Metabolite ID with Structure Assignment
EA401 Express MS – HLM
EA402 Express MS – RLM
EA403 MS – Liver Microsomes
EA404 MS – S9
EA405 MS – Hepatocytes
EA415 Express MS – MLM
EA416 Express MS – PLM
EA417 Express MS – DLM
EA419 Biomimetic Oxidation
When and why should I perform metabolite ID?
In addition to the fact that it is required by regulatory agencies, metabolite identification enables you to select the most appropriate non-clinical tox species based on exposure to all major human metabolites. Early in discovery/development, identification of soft spots can provide useful SAR information and guide chemistry efforts. This can help you design better molecules or optimize existing ones.
How does Absorption Systems perform metabolite ID?
Metabolites are generated using in vitro systems (microsomes, hepatocytes, S9 fractions) or in vivo (PK, tox, or clinical samples). We then utilize high-resolution mass spec coupled with data-dependent acquisition of MS(n) data. Depending on your study objectives, we can determine relative abundance of metabolites and perform definitive structure elucidation.
What are the benefits of biomimetic oxidation?
Biomimetic oxidation allows you to generate milligram quantities of metabolites for drug-drug interaction potential, enabling comprehensive safety evaluation. Compared to other synthesis techniques, biomimetic oxidation has fewer solubility limitations, allowing for larger quantities of metabolites to be generated.
Absorption Systems offers several streamlined and cost effective protocols for performing metabolite ID studies ranging from screening for metabolite profiling to complete structural elucidation depending on customer needs.
Our studies are performed by a dedicated professional staff with years of experience in the structural elucidation of drug metabolites and natural products.
Absorption Systems provides the whole spectrum of metabolite ID services from support of discovery phase studies through clinical bioanalysis. We have you covered from start to finish.