With over 60 years’ experience in biotransformation, Concept Life Sciences is the partner to support all your metabolite profiling and identification requirements. From eliminating metabolic ‘soft spots’ in support of early stage discovery activities to first in human/patient clinical studies to ensure in all in vivo human metabolites have safety coverage, our team has significant expertise in designing and interpretation of biotransformation data.
In early phase drug discovery, elimination of ADME liabilities is essential to progress a compound (cross reference in vitro ADME page). Metabolism studies provide context on parent compound stability, however the need to determine if structural similarities between compounds are prone to metabolism requires metabolite profiling. Rapid, untargeted analysis by LC-MS, with high resolution accurate mass, facilitates the detection of these metabolic ‘soft spots’ and can be fed back into Medicinal Chemistry programs to aid in compound design. This approach can also be applied to early stage PK studies, when an unexpected increase in clearance is observed in vivo.
As a compound moves closer to candidate nomination, cross species metabolite profiling and identification is often performed to determine if any unique or disproportionate human metabolites are likely to be formed. These comparative metabolism studies allow selection of pre-clinical species to support MIST, ICH M3 and other guidelines. Using a combination of LC‑UV-MS/MS and LC‑radioflow profiling (if a suitable [14C] or [3H] analogue is available), Concept Life Sciences provides quantitative (or semi-quantitative) data alongside the structural information obtained from the mass spectrometry. Where required these studies can be performed to GLP.
Once a clinical candidate is identified and enters First in Human/Patient Phase I studies, early investigation into human metabolism provides confirmatory evidence on unique and disproportionate human metabolites.
This information can be obtained from the samples already obtained for clinical PK (cross reference clinical bioanalysis page) and with Concept supporting both assay types, this data can be supplied in line with initial PK and as such the client does not need to perform a separate study.
For compound’s where structural elucidation can not be determined by LC-MS/MS, Concept offers reference standard synthesis through our synthetic chemistry department (cross reference synthetic chemistry page) or if sufficient material is available, NMR through our GLP NMR facility (cross reference GLP NMR page).
We process LC-MS data for all studies using instrument manufacturer’s data mining software to detect expected and unexpected metabolites. For regulatory studies, the software package has undergone computer system validation.