Metabolite Identification for Drug Discovery, IND-Enabling Safety, and Clinical Studies

Ricerca Biosciences, a partnered drug development organization, provides custom integrated in vitro and in vivo metabolism studies to support medicinal chemistry lead optimization programs, IND-enabling toxicology and pharmacokinetics studies, and clinical metabolism requirements. In addition, Ricerca conducts on-site metabolite and standards synthesis, including radiolabeled compounds. Sophisticated analytical tools employed by experienced metabolism chemists will facilitate structure modifications and help to design appropriate toxicokinetic and pharmacokinetic studies.

Metabolic Stability for Medicinal Chemistry Support

• Identifies Metabolically Labile Positions
• Guides Structure Modifications to Reduce or Eliminate Metabolism

Metabolite Identification for Lead Optimization

• In vitro Incubations with Microsomes
• Chromatographic Method Development
• Isolation and Purification as Needed
• Mass Spectrometry Analysis
• NMR Structure Elucidation

Metabolite Identification for IND-Enabling Studies

• In Vitro Profiles
  - Microsomes, S9, or Hepatocytes
  - Range of Species (Human, Rat, Dog, Monkey)
• CYP Inhibition and Inductions
• In Vitro Drug-Drug Interactions
• Synthesis
  - Derivative and Metabolite
  - Stable and Radiolabel Isotopes
• Structure Identification
  - Metabolism Chemistry Experience
  - Experts in MS Interpretation

Post-IND Metabolite Identification Support

• In Vivo Pharmacokinetics Studies
  - Mass Balance
  - Metabolite Profiles in Toxicology Species
  - Metabolic Pathway
  - Tissue Distribution
• Other Pharmacokinetics Studies

Major Equipment

• LC-MS/MS Equipment
• PE Sciex API-3000 (three units)
• PE Sciex API-365 (two units)
• PE Sciex API III Plus (one unit)
  (All Equipped with Shimadzu LC-10AT vp HPLC, On-line Degassing Systems,
  Ion Spray, Turbo Ion Spray, and APcI)
• Finnigan TSQ-700
• GC-MSD Systems
• Varian Gemini 300 MHz NMR
• Varian 750 MHz NMR at University of Akron and Varian 600 MHz NMR at
  Case Western Reserve University
• FT-IR
• HPLC Systems with Flow-through Radioactivity Detectors
• Liquid Scintillation Counters
• Gamma Counter