Because RMI utilizes modern high resolution mass spectrometers, we are able to provide assays where both quantitative and qualitative data are obtained. As a result of this capability we have constructed two combination assays that focus specifically on the needs of discovery research programs.
MSI Combo™, is aimed at the lead discovery/optimization phase.
This is when we conduct metabolic stability (in either microsomes or hepatocytes) using a QTOF, so we have full-scan accurate mass data, to generate the stability quantitative data. We can also extract information about metabolites that are formed, from the full-scan dataset using the accurate mass selectivity to determine what molecular formula changes have occurred. If full metabolite identification is required we re-inject the last time point and obtain the MS/MS data necessary to determine what sub-structural moiety has undergone the biotransformation.
The advantage of this tiered approach is that it only requires data-processing to generate a list of metabolites present in the sample. Also when full metabolite identification is deemed necessary there is no re-incubation, as the metabolite data is obtained from the same sample that was used for the stability experiment. In the past stability and MetID is often conducted in separate groups and they sometimes observe different % turnover of the compound, which hinders clear conclusions.
PKI Combo™, is also aimed at the discovery phase.
This is when we conduct discovery PK studies using a QTOF, so we have full-scan accurate mass data, to generate the PK quantitative data. Similarly as described above we can also extract information about metabolites that are formed, from the full-scan dataset. Also if full metabolite identification is required we can re-inject the last time point or a time-proportional pool and obtain the MS/MS data necessary to determine what sub-structural moiety has undergone the biotransformation.
These two combination assays enable a fuller comparison of in-vitro stability and in-vivo clearance since we can routinely include the metabolite information.
Since we have partnered with a local in-life facility we can provide full-service rodent PK (mouse and rat) analyses. Thus enabling us to address all aspects of the MSI and PKI combo analyses.