Metabolite Identification and Testing Services

Contact us to learn more about Apredica's metabolite profiling, synthesis, and toxicity testing services.

When a drug enters an organism it is subject to metabolism, resulting in the production of metabolites from the parent drug. However, metabolites can be toxic or pharmacologically active, just like drug candidates. Consequently, the FDA requires the identification of metabolites and their evaluation for safety (Guidance for industry, Safety testing of drug metabolites, FDA, February 2008). Before any NCE (New Chemical Entity) can be approved for clinical research, the NCE's metabolites must be identified and subjected to preclinical toxicity testing to ensure safety.

Because producing the metabolites needed for preclinical toxicity testing is costly and time consuming, metabolite identification, synthesis, and toxicity testing are generally reserved for the final stages of preclinical testing.

Apredica offers metabolite identification and production service. The process has three stages:

1. Metabolite identification
2. Metabolite synthesis
3. Metabolite toxicity testing

Metabolite ID

Compound Requirement: 3-5 mg

In vitro models available: liver microsomes, S9, hepatocytes, plasma (species: mouse, rat, dog, monkey, human, sex-specific available)

In vivo confirmation: mouse, rat routinely available; higher compound amounts are required

Deliverables:

• List of proposed metabolite molecular weights and spectra
• Hypothesis for structures of metabolites
• LC/MS/MS method for metabolite authentication
• Analytical profile of the parent + metabolites (optional)

At the completion of metabolite identification, the metabolites structures are discussed with the client's chemists and the decision made about synthesis and retesting of the metabolites.

Metabolite Synthesis

To proceed to IND, the safety of the NCE's metabolites must be assessed in preclinical testing. This testing, of course, requires production of sufficient amounts of the metabolite to support testing - requiring costly and time-consuming medicinal chemistry efforts.

In partnership with AsisChem, Apredica can synthesize up to a few grams of metabolites based on the metabolite identification data package. The experienced medicinal chemists at AsisChem design the chemical path to metabolite synthesis. Once the metabolites are synthesized, they are analyzed by the AsisChem-Apredica team, and matched to the original analytical metabolites' traces. Your metabolites are then ready for efficacy and safety testing.

Metabolite Toxicity Testing

Abundant metabolites may pose a safety risk and might need to be subjected to the same in vitro toxicity testing as the parent compound See details on Apredica's toxicity testing services.

Contact us to learn more about Apredica's metabolite profiling and toxicity testing services.