Search
Applications across therapeutic modalities
Accurate metabolite identification and localization are essential to understanding drug metabolism and ensuring regulatory compliance. Thermo Fisher Scientific’s application-focused solutions leverage intelligent data acquisition, multi-stage fragmentation, and streamlined workflows to deliver comprehensive insights with greater confidence.
Our tools enable detection of reactive metabolites, precise transformation site localization, and the integration of discovery and targeted analyses in a single experiment, accelerating your ability to characterize complex metabolic pathways efficiently.
Explore how our advanced applications support your critical analytical challenges from early discovery through late-stage development.
Labelled small molecule profiling and structural characterization
The investigation of a drug’s metabolic fate is an important component of the drug development process, to ensure its efficacy and safety. In particular, formation of metabolites that are capable of reacting with macromolecules (reactive metabolites) could contribute to drug-induced toxicity. For this reason, glutathione (GSH) trapping is a widely used assay for detection of these reactive metabolites during the lead optimization stage in the pharmaceutical industry.
Detection and identification of isotope-labeled glutathione trapped reactive drug metabolites
This application note showcases a streamlined solution using the Thermo Scientific Orbitrap Exploris 240 Mass Spectrometer and Thermo Scientific Compound Discoverer Software. This demonstrates an integrated approach for high throughput identification and structural characterization of GSH trapped metabolites utilizing liquid chromatography-high resolution mass spectrometry and efficient data processing.
Detection and structure elucidation of low abundant PROTAC drug metabolites
The identification of drug metabolites routinely relies on LC-MS experiments, with fragmentation data enabling their structure elucidation. In recent years, heterobifunctional small molecule drugs, acting on a given protein of interest (POI) through recruitment of inherent protein degradation pathways rather than inhibition, have gained significant interest as new modalities, with multiple-such proteolysis targeting chimera (PROTAC). However, due to PROTAC’s unique properties, the identification of their metabolites can be challenging.
Confident transformation site localization of PROTAC drug metabolites facilitated by multi-stage fragmentation LC-MS
This application note demonstrates characterization of drug metabolites from in vitro incubations of bifunctional PROTAC model drug compounds, and the utility of intelligently acquired MSn fragmentation data for transformation site localization and soft-spot analysis.
Streamlined process to acquire sample relevant MSⁿ data for deeper drug metabolite profiling with intelligent data acquisition
Rapid metabolism reduces the duration and potential efficacy of pharmaceuticals, so in early drug discovery stages, metabolic profiling 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 in some cases the intermediates in the drug metabolism can have toxic effects.
Increased confidence in drug metabolite identification through intelligent data acquisition strategies and multiple fragmentation techniques on the Thermo Scientific Orbitrap Tribrid Mass Spectrometer
This white paper highlights intelligent data acquisition technologies available, such as Thermo Scientific AcquireX Data Acquisition Workflow and real-time library search, which streamline the process to acquire sample relevant MS² and MSⁿ data for deeper drug metabolite profiling. Orthogonal fragmentation methods such as Ultraviolet Photodissociation (UVPD) can provide complementary fragments to allow determination of transformation sites for drug metabolites from structurally informative fragments.
Combine discovery and targeted workflows into a single experiment
Simultaneous QUAntitation and Discovery (SQUAD) analysis seamlessly combines discovery and targeted workflows into a single experiment, offering a more comprehensive and versatile solution. Leveraging Thermo Scientific mass spectrometers, SQUAD workflows are enhanced by the unique hardware and software solutions of these platforms. To enhance depth of discovery analysis, the AcquireX Data Acquisition Workflow optimizes the interrogation of relevant compounds by MS2, leading to greater coverage and more confident annotation when compared to traditional data-dependent analysis.
Amplify laboratory efficiency for known and unknown nitrosamines - Simultaneous QUAntitation and Discovery (SQUAD)
Watch this insightful on-demand webinar where we explore the cutting-edge SQUAD approach to nitrosamine and NDSRI testing. This innovative method focuses on confidently annotating and accurately quantifying a targeted set of compounds using authentic standards and calibration curves. Simultaneously, it performs untargeted analysis to identify novel impurities, all within a single injection, resulting in unparalleled laboratory efficiency.
For Research Use Only. Not for use in diagnostic procedures.