This is part one of a three-part series on Thermo Fisher Scientific’s analytical instrument solutions for metabolite identification in the small molecule drug development process.
Metabolite identification (MetID) is a crucial and integral part of traditional small molecule drug discovery and development. In this context, metabolism describes the breakdown and conversion of xenobiotics into molecules that can be excreted from the body, as shown in Figure 1. However, rapid metabolism reduces the duration and potential efficacy of pharmaceuticals, so in early drug discovery stages, metabolic profiling from in vitro studies is employed to identify metabolic soft spots to inform optimization of lead compounds to attain desired pharmacokinetics. Additionally, metabolic profiling plays a critical role in evaluating the safety of the molecule, as intermediates in the drug metabolism can have toxic effects. As a result, regulatory bodies have published detailed guidance on required testing. (See relevant FDA guidance).
As described in this application note from Kate Comstock, et al., the Thermo Scientific Orbitrap Exploris 240 mass spectrometer can provide straightforward and comprehensive metabolite profiling, allowing informed decision-making for lead optimization efforts. This is enabled by sensitive high-resolution accurate mass measurements, fast polarity switching and MS2 fragmentation capabilities of the Orbitrap Exploris 240 MS. This is complemented with the intelligent AcquireX data acquisition mode and advanced data processing in the Thermo Scientific Compound Discoverer software.
The application note further describes the data processing workflow with the Compound Discoverer software that effectively mines the data to enable metabolite profiling and identification using predefined processing templates. The software relies on both a targeted approach to detect predicted metabolites generated based on intelligent dealkylation/diarylation prediction and common metabolic pathways, as well as an orthogonal approach to identify unexpected or unknown metabolites based on isotopic pattern matching and compound class scoring.
Related information
Read the complete application note here and discover Thermo Fisher Scientific’s metabolite identification solutions on our website.
Blog Part 2 of 3: Advanced LC-MS Tools and Software Solutions to Ease Your Metabolite Identification Challenges
Blog Part 3 of 3: Leveraging LC-MS for Accurate Metabolite Identification (MetID) in Drug Discovery & Development
You can also find out more about Thermo Fisher Scientific cutting edge analytical instruments and software solutions to streamline and speed up any drug development processes in our Learning Center.
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