It’s never easy to catch all the great science presented at different conferences these days – so in case you missed it, and if MetID is your area of interest, you can now learn about and download the great posters that were presented at the Great Lakes DMDG 2024 meeting held at Purdue University in May below. The presented work highlights how drug metabolism and pharmacokinetics (DMPK) scientists are implementing Thermo Scientific technology and software to enhance and speed up their metabolite identification work.
The right combination of tools for MetID
The use of high-resolution mass spectrometry (HRMS) is a gold standard in the process of drug development, particularly in the identification of drug metabolites. The Thermo Scientific Orbitrap high resolution accurate mass (HRAM) mass spectrometers have been significantly impactful in this respect. With exceptionally high resolution across a range of different instrument configurations, and fast polarity switching to reduce experimental time, Orbitrap technology offers exceptional versatility for enhanced small and large molecule structural analysis. Coupling this technology with smart data acquisition and processing software brings a great benefit to a working MetID laboratory.
Don’t miss a thing in your research
The Thermo Scientific Orbitrap Exploris 240 mass spectrometer, known for its exceptional resolution and advanced data dependent acquisition capabilities, was employed to profile metabolites of selected commercial drugs. The utilization of AcquireX advanced data acquisition enabled the triggering of MS-MS for low-abundance metabolites that were otherwise masked by the matrix.
AcquireX advanced data acquisition workflows are designed to generate background exclusion lists and sample component inclusion lists. It updates the acquisition methods in real time in an automated fashion, improving the triggering of MS-MS of low abundant ions of interest and enhancing the quality and efficiency of metabolite analysis. This automated background exclusion further improves the efficiency of analysis and reduces development time.
See the results of the joint project between Amgen and Thermo Fisher Scientific exploring how AcquireX helped improve Amgen’s MetID process. Download the poster.
Improve quality and efficiency of metabolite identification
One of the key features of the Orbitrap IQ-X Tribrid mass spectrometer is its ability to use an intelligent data acquisition strategy known as the “Real-Time Library Search” (RTLS). RTLS compares experimental MS2 to a spectral library and generates a score based on similarity. It can then trigger additional scan behaviours, including MS3 or alternate fragmentation, based on compounds that meet the scoring criteria set in the method. This technology allows for the selective triggering of MS3 only on precursors with spectral similarity to the parent or compound(s) of interest, providing additional structural information on the most important compounds, while maintaining a high MS2 scan rate.
In a recent study with Gilead Sciences, the Orbitrap IQ-X Tribrid MS Met-IQ workflow was used, leveraging the real-time decision-making of new RTLS filter for metabolite profiling. The results showed that more metabolites were detected and MS3 scans triggered than using conventional DDA acquisition without RTLS. For instance, RTLS data acquisition accurately identified fragmentation level similarity within a low-abundant dealkylated metabolite of losartan. This metabolite was confidently identified based on MS3, HRAM, and fine isotope pattern.
Learn how Gilead Sciences used RTLS to guide data acquisition based on structural similarity and improve efficiency for metabolite identification. Download the poster.
The integration of RTLS on the Thermo Scientific Orbitrap Tribrid platform and AcquireX for automated background removal significantly enhances and facilitates metabolite identification. These advancements in data acquisition strategies represent a significant leap forward for drug development and metabolite profiling. They allow for a more efficient and precise identification and structural characterization of metabolites, improving overall data quality and enhancing usability in the process.
Related information
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Blog 1 in a series: Speed up Drug Development Process With Fit-for-Purpose Metabolite Identification Solutions
Blog 2 in a series: 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
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