Custom Metabolite Synthesis for Metabolite Profiling
Ensure you’re meeting regulatory drug metabolite requirements for safety with Charles River’s custom metabolite synthesis services. In the United States, FDA guidelines recommend that all human disproportionate drug metabolites accounting for greater than 10% of total exposure are assessed in safety studies. Our metabolite profiling chemistry team’s custom services deliver data packages that:
- Satisfy FDA recommended guidelines for safety assessment
- Enable clients to invest in the compounds with the best chance of safety and commercial success
Biomimetic Oxidation (BMO) for Metabolite Profiling
The Charles River synthetic chemistry team has developed a biomimetic chemical workflow to generate drug metabolites via late stage oxidation/de-alkylation. Using a screening panel to first identify the putative metabolites of your active pharmaceutical ingredients (APIs), we can then reproduce them rapidly, on scale, with detailed metabolite synthesis structure characterization.
A biomimetic workflow for metabolite synthesis includes the initial screen, reaction optimization and scale up. Typical optimization and scale up is completed in just four to six weeks (5-50 mg isolated) and five to seven weeks (50-500 mg isolated).
The BMO metabolite synthesis approach is a useful strategy for de-risking late stage drug discovery programs. The synthetic BMO approach allows rapid access to new polar analogues that expand the known structure-activity (SAR) relationship, with the added potential for metabolite identification of pharmacologically active metabolites. The discovery of these new polar compounds can potentially provide additional synthesis examples for patents at time of filing, for your compound patent protection.
Biomimetic Case Study: IMATINIB
See how metabolite synthesis, isolation and full characterization occurred in seven known metabolites of Imatinib, an oncology drug first approved by the FDA in 2002.
Bespoke Custom Synthesis of Metabolites
Where metabolic fates of APIs are known, our team will routinely design and execute multi-step synthesis in our state-of-the-art facilities for rapid results. All custom putative metabolites and metabolite synthesis services come with a comprehensive data package. Packages include analytical data provided up to GLP standard as required to facilitate metabolite synthesis regulatory submission, including a Certificate of Analysis specifying UPLC-MS purity and 1H-NMR (13-C, 19-F, 15-N and 31P-NMR as required).
Combining Discovery and Safety Delivers Best Met ID Outcome
When you choose Charles River for your metabolite synthesis and metabolite identification services, you also gain access to world-class analytical and safety teams. Working together, we ensure your lead candidate has a desirable safety profile and the highest chance of commercial success. As programs progress, the synthetic chemistry team can call upon colleagues in pharmaceutics and formulation, scale up chemistry, and safety assessment and IND-enabling studies.
Frequently Asked Questions (FAQs) for Metabolite Synthesis Services
How do you determine if the putative metabolites formed in your BMO screen are in fact the ones of interest?
Charles River’s metabolite profiling scientists work extensively with our dedicated analytical support staff to solve chemical structures and have a track record of successfully assigning structures to putative metabolites.
The teams also work extensively with the Charles River safety teams running metabolite ID and metabolite profiling studies. Daughter plates from the BMO screen allow direct comparison with real data generated in client studies, which can be compared directly with the putative metabolite oxidation set. Once we have confirmed a match of the metabolite of interest with a set of reaction conditions, we can rapidly optimize and scale up the appropriate reaction to deliver the required quantities to satisfy the metabolite identification project. Request a consultation with our structure elucidation team.
Does Charles River provide a Certificate of Analysis (CoA) with putative metabolites?
We can provide a CoA up to GLP standard as required. Upon quote request, please specify your reporting and certification, US FDA requirements or other safety requirements so we can accurately quote metabolite synthesis timelines and costs.
How do you isolate and purify chiral compounds?
In the hands of our expert purification scientists, the right purification technologies allow us to exceed your expectations for quality and turnaround. Our on-site analytical and preparative systems for both chiral HPLC and super critical fluid chromatography (SFC) are managed by a team of experienced separation scientists with a track record of successfully providing separation of chiral analytes from complex mixtures and metabolite synthesis services.
Purification of metabolite reactions is often difficult. How do you achieve isolation of a single entity from complex mixtures?
Metabolite oxidation products of chemical oxidation or microbial digestion are often complex in nature, with HPLC running times very close to the parent structure. Following a metabolite synthesis BMO screen, our skilled metabolite profiling scientists first optimize reaction profiles to minimize side product formation. Then, with access to high-throughput purification screening systems that can rapidly identify optimal separation conditions, our dedicated purification scientists handle the purification process.