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Optimizing the metabolic profile of a target compound and mitigating toxicity risk are central to effective drug discovery. At IRBM we implement three workflows to support these efforts:

  • Tier I MetID workflow – a screening assay that uses cellular or sub-cellular fractions, such as liver microsomes, to identify the main metabolic soft spots of newly synthesized compounds
  • Tier II MetID workflow – can be used for selected compounds and includes in vitro incubations (e.g., liver microsomes and hepatocytes) and in vivo studies in preclinical species
  • Metabolite radio-profiling – used to quantify radio-metabolites in biological matrices from in vivo preclinical studies

At IRBM, in vitro and in vivo Met ID are performed using a UHPLC-Orbitrap-HRMS. Metabolite radio profiling is performed using a UHPLC system coupled to fraction collection and microplate scintillation counting (UHPLC–FC–MSC).

In addition to metabolite identification, isolation, and production, using both microsomal or microbial incubation, the team has extensive experience in characterizing reactive metabolites such as glutathione and potassium cyanide adducts.

Identification and characterization of small molecules and peptide metabolites from HRMS raw data is conducted and supported by bioinformatics tools such as BioPharma Finder; Compound Discoverer; MetabolitePilot, as well as instrument agnostic software (Mass-MetaSite).

The Biodistribution, Biotransformation and Analytical Science team also supports early pre-formulation work for small molecule and peptides. The team can also carry out the characterization of the physicochemical properties of monoclonal antibodies and other large molecules.

Examples of Physicochemical and characterisation studies:

PHYSICOCHEMICAL STUDIES

  • Solubility (kinetic, thermodynamic, FaSSIF, FeSSIF and FaSSGF)
  • Stability (buffer, pH, etc.)
  • Lipophilicity (LogP, LogD and pKa)

LARGE MOLECULES CHARACTERIZATION

  • Aggregation
  • Fibrillation
  • Unstressed and Stressed Developability
FIND OUT MORE ABOUT OUR CROSS FUNCTIONAL DRUG DISCOVERY SERVICES

ADME/
PHARMACOLOGY

PK, PD AND
BIOANALYTICS

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