In traditional drug discovery, ADME work was not performed until after a compound had been selected as a potential drug for further development.  However, as 50-60% of compounds fail to make it to the market due to poor ADME/Tox properties, critical time was being lost by these "late" drug failures.

To overcome this problem, scientists are beginning to studya compund's ADME properties earlier in the drug development process, even as early as the drug discovery stage.  While this shift has the enormous potential benefits of reducing the time and cost required to bring a drug to market, this new philosophy significantly impacts the number of compounds that must have their metabolic profiles characterized.

Due to its excellent sensitivity and the large amount of quality data it produces, LC/MS has become the favored method for characterization of drug metabolites.  As the leader in the field of mass spectrometery research and development, Thermo Fisher Scientific has developed hardware and software tools to speed the process of metabolite profiling.  Thermo Fisher Scientific offers both triple quadrupole and quadrupole ion trap mass spectrometers, as well as the newest, breakthrough hybrid mass spectrometers.  In addition, various software packages are available to assist in metabolite identification.

With unsurpassed ruggedness, full-scan MS/MS sensitivity and data dependent scanning abilities, the  LTQ XL^TM and the  LCQ Fleet^TM  are the ultimate instruments for metabolite profiling.  The LTQ XL has the ability to automatically target relevant ions for MS/MS and MS to the Nth analyses and greatly simplifies the determination of sites of metabolism and structures of metabolites.  Triggering the acquisition of MS/MS and MS to the Nth scans via Thermo Scientific's exclusive Data Dependent™ feature allows researchers to collect critical data on both known and unexpected metabolites.  Additionally, the LCQ Fleet can easily analyze drugs in such complex and dirty matrices as plasma, urine, and bile.

When quantitation of drug metabolites is necessary Thermo Fisher Scientific offers the  TSQ®Quantum Series.  The TSQ Quantum has the lowest detection limits of any triple quadrupole instrument available today and can provide both high-resolution parent and product scans.  Also equipped with a rugged orthogonal source, the TSQ Quantum provides extremely reproducible data in plasma, urine, and bile.

To assist in turning these data into the results needed to drive further drug development, Thermo Fisher Scientific offers various software packages, MetWorks^TM Metabolite Identification Software    and Mass Frontier™  .  MetWorks is designed for processing drug metabolism data and automatically extracts out reconstructed ion chromatograms of major and minor metabolites.  To help find unexpected metabolites, MetWorks uses a cross-correlational algorithm that compares parent drug MS/MS data against MS/MS data of potential metabolites. Spectra with high correlation values are likely to be drug metabolites.

Mass Frontier software assists in the management and interpretation of mass spectra. Its powerful and unique algorithms accurately predict the fragments and mechanisms resulting from mass spectrometric analysis of any compound.  Additionally, it has an exclusive classification algorithm using a principle components method to determine structure, properties and class membership of unknowns.

With this comprehensive set of tools for solving your ADME/Tox needs, Thermo Fisher Scientific has shown once again why it is the leader in mass spectrometry technology.

Below are links to recent drug discovery related application notes in PDF format. Please select a link to view/download the respective application note.