Metabolite Identification

Type:Services
SUBTYPE:Metabolism
SPECIES:
APPLICATION & SPECIALITY USES:ADME-Toxicology Products and Services
Keywords:Metabolic ProfilingMetabolismMetabolite Identification

OPTIONS:

We help our clients predict the human in vivo metabolites of their compounds throughout drug discovery and development programs. Data from our in vitro models informs their lead selection and optimization decisions and helps them design clinical and safety studies.

We recommend the following models based on the rate of compound clearance and length of study required:

  • Suspended Hepatocytes: High uptake and clearance compounds
  • HEPATOPAC Culture: Low uptake and clearance compounds / long-term studies.

Suspended Hepatocytes

In our suspended hepatocyte model we identify / profile metabolites by incubating the test compound in triplicate in four species (human, mouse, rat, and dog) of suspended hepatocytes. We typically include the time points: 0, 15, 30, 60, 120, and 240 minutes. A positive and negative control is included. Samples are collected and stored at ≤ 70°C for analysis by clients who prefer to do analyses in-house or by our partners using UPLC-MS/MS. Our report includes an analysis of sub-structural localization of the biotransformations observed.

Additionally, positive control samples are analyzed  for disappearance of parent, to demonstrate the metabolic competence of the system.

HEPATOPAC Culture

We use HEPATOPAC Technology to create stable hepatocyte cultures that can remain viable for up to 28 days. We recommend HEPATOPAC cultures for compounds that have low uptake and clearance and any experimental design requiring long-term viable hepatocyte cultures. Because of their longevity and stable enzymatic functions, HEPATOPAC cultures allow for the complete metabolism of pharmaceutical compounds. Compared to conventional systems, the HEPATOPAC model has demonstrated improved IVIVC in detecting primary and secondary excretory metabolites and is capable of identifying metabolites that may not be present in a short-term culture. HEPATOPAC cultures are available for the following species: human, rat, dog, monkey, and multi-species plates.