Metabolomics & lipidomics

Gain deeper, more reliable insight into complex biological systems with the Orbitrap Excedion MS. Reduce ambiguity and increase confidence in every result with high-resolution, accurate-mass performance and extended dynamic range that help enable precise metabolite identification and quantitation - even in highly complex samples.

 

Uncover meaningful biological patterns and quickly translate findings into actionable insight. Whether you’re performing broad, untargeted profiling or targeted analyses, benefit from clarity, consistency, and confidence to accelerate discovery and drive better decisions.


Untargeted discovery with eDR to unlock deeper insights

Detect up to 6× more compounds at the MS¹ level - where each compound is defined as a unique m/z–retention time pair after background subtraction, with isotopes, adducts, and in-source fragments consolidated into a single feature.

eDR increases plasma coverage across representative plasma-equivalent loads. SRM 1950 plasma extracts were analyzed with AcquireX deep scan workflow at 0,58, 1,44, and 4,33 µL plasma equivalent loaded on column using matched eDR and conventional full-scan acquisition. (A) Quality-filtered MS1 compound entities with filters: CV <20%, formula assignment, and peak rating >6 in all three MS1 reference replicates. (B) Strict mzCloud MS/MS matches with filters: CV <20%, non-blank formula assignment, peak rating ≥6 in 3/3 MS1 reference replicates, best mzCloud match score ≥60, and MS2 purity >60.

Following iterative injections, mzCloud spectral matching enables over 70% more compound annotations, significantly increasing identification confidence and biological insight.

 

Precursor inclusion lists for the data-dependent workflow are generated from full-scan MS¹ data acquired either with the eDR workflow or standard Orbitrap full-scan mode (without eDR), with results processed in Compound Discoverer 3.4 software for streamlined, high-confidence analysis.

Improved dynamic range of detected compounds with eDR

eDR scan mode achieves an additional order of magnitude of depth for plasma metabolite identification, when plotting a regression of peak area versus total number of compounds detected in SRM 1950. This demonstrates that the >6× increase in detected compounds is driven by enhanced sensitivity at the low end of the dynamic range - while preserving accuracy and performance for high-abundance species.

Improved sensitivity of low abundant compounds with enhanced dynamic range (eDR)

Highlighting its ability to reveal low-abundance species otherwise missed, this compound was annotated in plasma exclusively using the eDR scan mode.

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Annotated compound found in plasma only when using eDR scan mode. The mass spectrum on the bottom right indicates that A0 and A1 peaks are measured and can be used to further confidently confirm the molecular formula of the species as C19H40N3O9P [H]+.

The Orbitrap Excedion Pro MS delivers superior clarity: minimizing in-source fragmentation

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Full MS spectrum of Phenylalanine in plasma with fragment-to-precursor ratio reduced to 14% (with mild-trapping on).

What customers are saying about quantitative accuracy for metabolic research

"Mass spectrometers with extended dynamic range offer a significant advantage by enabling the simultaneous analysis of both trace-level and highly abundant analytes without signal saturation or the loss of low-intensity peaks. This perspective will benefit the analysis of biological, environmental, and industrial samples with a broad range of analyte concentrations. By improving isotopic and adduct distribution analysis and enhancing detection limits, such advanced mass spectrometers can significantly improve quantitative accuracy, making them indispensable for high-precision analytical applications."

 

Dr. Oliver Fiehn
Director, West Coast Metabolomics Center, UC Davis Genome Center

Advance your metabolomics analyses with the Orbitrap Excedion Mass Spectrometer

Dramatically expand detectable feature space, enabling more comprehensive coverage of the metabolome, with the enhanced dynamic range (eDR) function. By capturing substantially more low-abundance compounds without compromising data quality, eDR supports deeper insight into pathobiochemical processes and strengthens the ability to identify potential biomarkers in clinical research.

 

This increase in detected features directly translates into more confident identifications, as evidenced by higher numbers of online library hits and in-house spectral matches—ultimately delivering richer, more actionable metabolomic insight.

Positive ionization mode

When benchmarking conventional full-scan performance (no eDR), the Orbitrap Excedion MS delivers a substantial increase in both detected and annotated compounds compared to the Q Exactive MS - highlighting improved sensitivity and greater metabolome coverage even without eDR enabled.

Number of detected compounds (grouped features) and annotated species (mzCloud hits) in dried blood spot samples (n = 5) acquired in positive ionization mode.

 

Demonstrating a step-change in both detection capability and annotation power, with eDR enabled, the total number of detected compounds increased by 798%, alongside a 139% rise in mzCloud hits compared to the Q Exactive Mass Spectrometer.

Benefits of eDR in clinical research

By effectively reducing the dominance of high-abundance interferents such as EDTA, the eDR function mitigates one of the most persistent challenges in clinical metabolomics: matrix-driven ion suppression. Lowering the EDTA signal improves overall signal-to-noise for co-eluting analytes, enabling more reliable detection of clinically relevant features.

 

In plasma prepared with anticoagulants like K₂EDTA, residual EDTA co-elutes with endogenous metabolites and can saturate the detector in conventional full-scan mode. This leads to ion suppression, reduced sensitivity, and inconsistent detection of lower-abundance compounds.

 

With eDR, EDTA saturation is significantly reduced, restoring dynamic range and enhancing sensitivity for co-eluting metabolites. As a result, key biomarkers such as leucine/isoleucine (Leu/Ile), acetylcarnitine (CAR 2:0), and threonyl-aspartic acid (Thr-Asp) are detected with improved signal-to-noise and greater consistency - supporting more confident, reproducible clinical insights.

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Comparing conventional Orbitrap full-scan acquisition (eDR OFF) with enhanced dynamic range acquisition (eDR ON) demonstrates that eDR markedly improves signal-to-noise for compounds that co-elute with EDTA, including Leu/Ile [M+H]⁺, CAR(2:0) [M+H]⁺, and Thr-Asp [M+H]⁺. At the same time, eDR effectively suppresses the dominant EDTA signal, reducing saturation effects and restoring detection sensitivity for co-eluting analytes.

What scientists are saying about higher coverage for metabolic research

"In a clinical research setting, having reliable and robust work-horse instruments is crucial. Additionally, Increasing the number of identified metabolites is essential to understand the full biochemical picture of diseases and pathological states."

 


Katja Benedikte Prestø Elgstøen

Ph.D., Head of Section and Core Facility, Section for Metabolomics and Lipidomics, Department of Medical Biochemistry, Clinic of Laboratory Medicine, Oslo University Hospital

Cellular-Resolution lipid imaging of a mouse brain using the Orbitrap Excedion MS

Delivering precise molecular information with cellular-level detail, the Orbitrap Excedion MS is a powerful solution for spatial lipidomics. High resolving power and sub-ppm mass accuracy enable confident separation and identification of closely related lipid species across a broad mass range (m/z 250–1000), while its dynamic range and sensitivity ensure detection of both, abundant and low-level molecular species.

 

In spatial lipidomics, the challenge isn’t generating data - it’s generating data you can trust. Overlapping species, limited dynamic range, and insufficient spatial resolution often obscure biologically meaningful insight. Molecular distributions align with H&E histology, reinforcing confidence in spatial accuracy. The result: confident identification, clear biological differentiation, and spatially precise molecular insight — without compromise

High-resolution mass spectrometry imaging (MSI) of a horizontal mouse brain section

An RGB overlay of three selected m/z channels (m/z 772.5264, green and 848.6386, blue) acquired in positive-ion mode (m/z 250–1000) at 5 µm pixel size reveals distinct lipid distributions across the cerebrum and cerebellum, including clear visualization of the Purkinje cell layer (m/z 872.5575, red).

With the AP-SMALDI5 AF ion source coupled to the Orbitrap Excedion MS, researchers achieve 5 µm lipid mapping, clearly delineating brain regions and ingle-cell structures, including the Purkinje layer.

 

High resolving power and sub-ppm mass accuracy separate closely related lipid species, while exceptional sensitivity and dynamic range ensure detection of both abundant and low-level molecules across m/z 250–1000.

Advancing Spatial Lipidomics: Insights from Researchers

"The combination of high-resolution atmospheric-pressure MALDI with the Orbitrap Excedion Mass Spectrometer allows us to visualize, for example, lipid distributions in brain tissue with remarkable spatial precision and mass accuracy. The ability to clearly resolve even the Purkinje cell layer demonstrates how high resolving power and stable performance translate directly into biologically meaningful insight."

 

 

Bernhard Spengler Ph.D.

Professor of Analytical Chemistry, Justus Liebig University Giessen, Germany and

Director of the Center for Mass Spectrometric Developments, TransMIT GmbH, Giessen, Germany


Drug Metabolite Profiling & Identification (MetID)

For Pharma DMPK and MetID, the Orbitrap Excedion MS delivers confident detection, structural elucidation and quantitation of drug metabolites across small molecules and emerging modalities like synthetic peptides and oligonucleotides. With enhanced dynamic range (eDR) and high sensitivity, the Orbitrap Excedion MS enables reliable identification of low-level and unexpected metabolites in complex biological matrices to support informed development decisions.

 

Reduce in-source fragmentation and enhance metabolite integrity for DMPK/MetID analysis

In Pharma DMPK and MetID workflows, the challenge isn’t generating data - it’s confidently detecting and identifying low-level or unexpected metabolites in complex matrices.

 

The Orbitrap Excedion MS enables sensitive detection, structural elucidation, and quantitation across small molecules and emerging modalities such as peptides and oligonucleotides. Enhanced dynamic range (eDR) and sensitivity reveal low-abundance metabolites that might otherwise remain hidden, enabling more confident metabolite characterization and development decisions.

 

eDR unlocks confident detection of low-abundance semaglutide in micropig plasma

With eDR enabled on the Orbitrap Excedion MS, the intact semaglutide signal is clearly resolved from the complex plasma background, exhibiting a well-defined isotopic envelope and accurate charge-state assignment. Zoomed spectra show enhanced signal-to-noise and cleaner isotopic patterns, enabling confident detection and identification of this low-abundance therapeutic peptide. In contrast, without eDR, spectral clarity is compromised by interference from high-abundance matrix ions.

 

By extending the effective dynamic range within a single scan, eDR minimizes the impact of dominant background ions that would otherwise obscure low-intensity species. Combined with the high mass accuracy and resolving power of the Orbitrap Excedion MS, this enables confident detection, characterization, and quantitation of trace-level biotherapeutics in complex DMPK samples.

Confident detection of low-abundance intact semaglutide (GLP-1 analog) in micropig plasma, collected 20 minutes post subcutaneous dosing, is enabled by enhanced dynamic range acquisition (eDR ON) on the Orbitrap Excedion MS. Compared to standard full-scan acquisition (eDR OFF), eDR delivers clearer signal discrimination from the plasma background, supporting reliable identification of this trace-level therapeutic.

High-sensitivity, selective quantification of ASOs in plasma

Quantifying low-level antisense oligonucleotides (ASOs) in plasma is challenged by complex background and limited selectivity. The Orbitrap Excedion MS addresses this with HRAM HCD MS/MS and multiplexed fragment-ion quantification, enabling higher sensitivity and confidence.

 

By summing multiple fragments in tMS2, signal response increases by up to 75%, significantly improving signal-to-noise. The method achieves a 100 pg/mL LOQ with excellent linearity (R² ≈ 0.999) and robust precision across a wide dynamic range.

 

With high resolving power, sub-ppm mass accuracy, and enhanced dynamic range, the Orbitrap Excedion MS cleanly separates ASO signals from plasma interferences—delivering reliable performance for regulated bioanalysis and pharmacokinetic studies.

Sensitive, high-confidence quantification of antisense oligonucleotides (fomivirsen and nusinersen) in human plasma is achieved using HRAM HCD tMS² on the Orbitrap Excedion MS. Summing multiple fragment ions boosts signal response by 40–75% versus single-ion detection, enabling a 100 pg/mL LOQ with excellent linearity, precision, and accuracy across three orders of dynamic range.

Environmental and food safety research

For Environmental and Food Safety (EFS) research, the Orbitrap Excedion MS enables sensitive detection and confident identification of known and emerging contaminants in complex matrices. With extended dynamic range and high-resolution accurate-mass performance, the Orbitrap Excedion MS supports both targeted quantitation and comprehensive non-targeted screening to deliver reliable, decision-grade results.

 

Significant sensitivity increase with eDR scans

eDR helps push detection and quantitation into trace level ranges that matter for food and environmental monitoring while maintaining confidence in the measurement.

 

The following figure demonstrates a challenging food matrix, emamectin B1a in leek at 0.010 mg/kg, or 10 ppb. It shows increasing significant sensitivity with eDR scans.

Data courtesy of Prof. Amadeo Fernandez-Alba

What scientists are saying about qualitative and quantitative performance for EFS sample analysis

"With the Orbitrap Excedion MS, we can finally bring high-resolution mass spectrometry into our pesticide lab and rely on it day in and day out—gaining the confidence, selectivity, and consistency we need for accurate results."

 

 

Amadeo R. Fernandez-Alba Ph.D.

Professor of Analytical Chemistry at the University of Almeria

“eDR is a game-changer, delivering far more detected compounds and much higher sensitivity—enabling sub-ppt PFAS quantitation alongside comprehensive non-targeted analysis in highly complex samples on a single, versatile platform.”

 

Lee Ferguson, Ph.D.

Professor of Civil and Environmental Engineering at Duke University 


Biopharmaceutical: Versatility for characterizing different molecular domains

The Orbitrap Excedion Pro BioPharma Mass Spectrometer ensures comprehensive characterization by detecting and quantifying impurities and modifications, performing accurate quantitative analysis, and enhancing top-down, middle-down, and bottom-up capabilities. It streamlines workflows for rapid, high-throughput analysis, significantly reducing time-to-results and increasing productivity.

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UHPLC-HRAM-MS-ddMS2 analysis of NISTmAb tryptic digest peptide mapping experiment, EThcD unambiguously identified the two leucine residues (loss of 43Da from z9 and z12 fragments) and one isoleucine residue (loss of 29Da from z6 fragments) in this 13-amino acids doubly charged peptide with complete sequence coverage. Zoom-in insets show high mass accuracy (<5ppm) achieved for the signature fragments.

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Signature fragments (c+57 and z-57) generated by ETD distinguish isoaspartic acid from aspartic acid.b: In a UHPLC-HRAM-MS-ddMS2 analysis of NISTmAb tryptic digest peptide mapping experiment, EThcD achieved high sequence coverage and unambiguously identified isoaspartic acid in a 23-amino acid triply charged deamidated peptide present at a low abundance level (0.18%) with high confidence. The zoom-in insets showed the high mass accuracy (<8 ppm) achieved for both signature fragments (z6-57 and c17+57).

What customers are saying about the value to their biotechnology work

"The Orbitrap Exploris 480 MS has been indispensable for biotherapeutic characterization, running continuously in our lab and producing high-quality data. The Orbitrap Excedion Pro Biopharma MS enhances this platform through the addition of electron transfer dissociation (EASY-ETD) and an extended mass range. Initial data shows that high spectral acquisition rate of EASY-ETD results in deeper protein sequence coverage, improved PTM characterization, detection of large aggregate impurities, and richer fragmentation patterns for confident disulfide linkage assignments. These improvements provide immediate value to our biotechnology work and will serve as our next generation platform."

 

Dr. Andrew Mahan
Associate Director and Mass Spec Group Leader
Johnson & Johnson Innovative Medicine


Structural biology: A novel workflow for higher order structure characterization

The Orbitrap Excedion Pro Biopharma Mass Spectrometer-based HDX MS offers a comprehensive and novel tool set for the analysis of protein conformation, conformation dynamics, and protein-protein interactions:

  • High sensitivity and scan speed enable in-depth coverage for Data-dependent acquisition (DDA) and Data-independent acquisition (DIA) workflows using Hydrogen deuterium exchange mass spectrometry (HDX-MS)
  • 100% sequence coverage with 7.5 redundancy for HC and 5.2 for LC of monoclonal antibodies or antibody-drug conjugates can be achieved in 6 min with loads as low as 300 ng
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Peptide identification and sequence coverage of Rituximab heavy chain (HC) and light chain (LC) across different on-column injection amounts (300 ng, 700 ng, and 1.5 µg) using a 6-minute gradient. The bar graph represents the number of identified peptides for HC (dark blue) and LC (light blue), while the orange line indicates sequence coverage percentage.

Optimized DIA workflow for high-throughput HDX-MS analysis

The fast scan speed of the Orbitrap Excedion Pro Biopharma Mass Spectrometer enables precise and high-throughput HDX-MS analysis, facilitating accurate protein-ligand binding screening.

Identification of binding pocket on KRAS G12C upon Adagrasib binding using DIA-HDX. (a) Woods plot. X-axis denotes the residue number, while y-axis shows percentage change in deuteration. Blue bars with error bars indicate experimental data points at 20sec labeling time, representing regions with significant deuteration changes. Dashed lines indicate a threshold for significant changes in deuteration. (b) Structural representation of KRAS G12C in complex with Adagrasib. The protein backbone is depicted in gray, with the G12C mutation region and key structural elements highlighted in blue.

What customers are saying about HDX-workflows

"The Orbitrap Exploris 480 MS has been essential for our high-throughput HDX-MS workflows, consistently delivering reproducible and reliable peptide-level deuterium uptake data. The Orbitrap Excedion Pro Biopharma mass spectrometer further enhances this capability with exceptional sensitivity, optimized low-flow setup, and advanced data-independent acquisition (DIA) strategies. Our initial evaluation demonstrated high-quality peptide-level resolution and improved detection of low-abundance peptides, enabling more comprehensive and precise characterization of protein-ligand and protein-protein interactions. These advancements make the Orbitrap Excedion Pro Biopharma MS an invaluable platform for next-generation HDX-MS studies."

 

Dr. Malvina Papanastasiou
Group Leader, Research Scientist, Broad Institute of MIT and Harvard


Proteomics: Proteome profiling with depth, accuracy and precision

Proteomics workflows often force tradeoffs between depth, speed, and quantitative confidence - especially in complex samples. The Orbitrap Excedion MS eliminates these compromises, enabling confident identification and quantitation of proteins and peptides with high-resolution, accurate-mass performance and extended dynamic range.

 

Whether you’re tackling low-abundance targets or highly complex matrices, Orbitrap Excedion MS delivers the sensitivity and selectivity needed to uncover meaningful biology - without sacrificing throughput or data quality.

 

Designed to accelerate both discovery and translational research, it provides deep proteome coverage, robust and reproducible quantitation, and reliable structural insight - so you can move from data to decisions with confidence.

 

Robust identification in DIA mode

Even in realistic, mixed-species samples, Orbitrap Excedion MS maintains strong identification performance. The graph below highlights the average total number of proteins identified across human, yeast, and E. coli components—demonstrating consistent depth and reliable performance in complex proteomic workflows.

These graphs show DIA performance using a 3proteome mix and a 50 cm μPAC Neo Plus column.

Select throughput settings based on study needs without losing confidence in quantitation

Median protein log₂ ratio deviations ≤0.10 across yeast, human, and E. coli proteomes

Consistent, high-accuracy quantitation across a wide range of SPDs using a 500 ng load on a 50 cm μPAC Neo Plus is demonstrated. Even at high throughput (96 SPD), the Orbitrap Excedion MS quantifies over 5.5K proteins and 26K peptides, while scaling up to more than 11.8K proteins and 120K peptides at 12 SPD – delivering uncompromised depth and speed.

 

Across yeast, human, and E. coli proteomes, median protein log2 ratio deviations remain at or below 0.10, demonstrating tight, reliable quantitation you can trust for comparative studies.

What scientists are saying about identification and quantitative accuracy for proteomics sample analysis

"In the current environment, finding the cash for a new instrument is extremely difficult. The ability to upgrade instrumentation, at a fraction of the cost, is a game changer. It will allow many more labs to stay at the forefront of technology."

 

Danielle Swaney, Ph.D. Associate Professor, School of Pharmacy, Bioengineering, UCSF, Protein interaction mapping

Targeted and discovery proteomics

The Orbitrap Excedion Pro MS transforms everyday proteomics into exceptional results.

  • Accurate quantification with extended dynamic range
  • Hybrid-DIA, Parallel reaction monitoring (PRM) and DIA in a single experiment
  • Post-translational modifications analysis with EThcD fragmentation
  • Immunopeptidomics with EThcD fragmentation
  • Deep proteome coverage
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Sequence coverage of all Peptide spectrum matches (PSMs) when using either HCD fragmentation or EThcD fragmentation. Sequence coverage was calculated by matching theoretical fragments with 10 ppm mass accuracy and confirming the charge state.

Sample: Immunopeptides from Jurkat cells, courtesy of Dr. Albert Heck.

What scientists are saying about error-prone immunopetidomics research

"EThcD fragmentation on the Orbitrap Excedion Pro Mass Spectrometer boosts peptide sequence coverage, minimizing detrimental sequence gaps, even for peptides with unfavorable physicochemical properties, allowing less error-prone immunopeptidomics, glycoproteomics and de novo sequencing."

 

Dr. Albert J.R. Heck
Professor of Pharmaceutical Sciences, Biomolecular Mass Spectrometry and Proteomics
Utrecht University, The Netherlands


Our general purpose product lines are not intended for in vitro diagnostic purposes in accordance with our product documentation, manuals, and labels. They are designated for General Laboratory Use Only.

 

Our general purpose product lines have not been tested or validated for such applications and their use for in vitro diagnostic purposes may result in health and safety risks.

 

The product is For General Lab Use Only - Not For Diagnostic Procedures. The application is For Research Use Only - Not For Use In Diagnostic Procedures.

The Thermo Scientific Orbitrap Exploris and Excedion series mass spectrometers are Orbitrap instruments with an atmospheric pressure ionization (API) source for liquid chromatography (LC) mass spectrometry (MS) high-throughput applications. The instruments are designed to be placed on a bench in the laboratory and maintain mass accuracy across chromatographic peaks, supporting confident identification and quantitation using high-resolution accurate-mass detection.