CDoT’s analytical and absorption, distribution, metabolism, and excretion (ADME) group uses mass spectrometry based assays to:
- determine properties inherent to molecules such as solubility or lipophilicity,
- measure behavior in industry-standard ADME models, and
- characterize bio-molecular interactions
The group also supports characterization, small molecule QC, and mass-directed purification systems used by medicinal chemists, and assists with outsourcing and analyzing ADME and DMPK assays which are not available in-house.
Mass spectrometry-based assay development
A suite of high-end mass spectrometers, all with ultra-high pressure liquid chromatography (UHPLC) front ends, are utilized to develop assays for a variety of endpoints. These systems can be utilized to characterize bio-molecular interactions including noncovalent binding, covalent modification, and enzymatic reaction.
CDoT's ADME team currently offers the following industry-standard assays for initial predictions of small molecules' in vivo behavior:
- Aqueous solubility (with and without DMSO co-solvent)
- Solubility in assay-specific buffers
- Log D, pH 7.4
- Cell permeability
- Plasma stability and plasma protein binding (human/mouse/rat)
- Microsomal stability (human/mouse/rat/dog/monkey)
- Hepatocyte stability (human/mouse/rat/dog/monkey)
- Metabolite identification
- Intrinsic reactivity with GSH
- CYP inhibition
- CYP reaction phenotyping
For additional in vitro ADME assays not performed in-house (e.g., nuclear receptor reporter assays, uptake and efflux transporter assays, in vivo rodent pharmacokinetics), the ADME group will coordinate the interaction with contract research organizations (CROs).
Open Access Small Molecule Characterization
The analytical group maintains a group of instrumentation set aside for walk-up use by chemists to enable on-demand characterization of synthesized material. The analytical group also provides training on instrument operation and help with method development.
Inquiries about Analytical Chemistry and ADME group’s capabilities can be made by emailing