ADME Analysis
ADMETRx often assists its customers with their ADME analysis, particularly with more problematic compounds or difficult assays that require more processing or analysis time.
In addition to our higher levels of integrative modeling, we also perform industry-standard in vitro ADME profiling, including
- Solubility - HPLC/MS determination of solubility in aqueous buffers at pH 3 and 7 (including other pH values upon request) from DMSO stock; also including mixed aqueous systems such as simulated intestinal fluid, surfactants, and organic co-solvents. Quantitative evaluation of stability in aqueous buffers, simulated intestinal fluid is also available. Equilibrium studies from solid sample are available upon request. A solubility panel to evaluate potential formulation strategies is under development.
- Permeability - Quantitative evaluation of bidirectional transport across Caco-2 and MDCK cell monolayers, analyzing both passive and active components; novel methods for assessing permeability of highly insoluble compounds.
- Transporter Characterization - Assessment of potential active transport and associated transporters, using Caco-2 monolayers and specific chemical inhibitors.
- Metabolic Stability - Qualitative evaluation of stability of a compound after incubation with mouse, rat, or human hepatic microsomes, single time-point or time course (t½) and estimation of intrinsic clearance, examining both Phase I and Phase II mechanisms; other species and tissue microsomes available, as well as plasma stability.
- Metabolic Inhibition - Quantitative assessment of CYP inhibition (IC50) by compounds of interest against known standards, in rat hepatic microsomes.
- Protein Affinity - Measured via retention over human serum albumin (HSA) column using HPLC/MS, or by ultracentrifugation methods with rat or human serum.
- Partition Coefficient (Log P/Log D) - Octanol/water partitioning using LC/UV/MS detection for accurate concentration determinations in both phases over the log range of -3 to +3.
- pKa - Quantitative determination of thermodynamic dissociation constants for acidic, basic, and zwitterionic compounds using pressure-assisted capillary electrophoresis over the range of pH 3 to 10.
ADMETRx continues to focus on the next generation of drug discovery challenges. We are developing new methods today to meet your emerging needs.