MassMetaSite is an established approach for the automatic identification of metabolites for small molecule and peptides using Liquid Chromatography – Mass Spectrometry, UV, fluorescence, and radio-chromatogram data, reducing manual analysis from several hours to only a few minutes per compound. The program can assign chemical structures to each automatically detected chromatographic peak based on the MS and MS/MS fragmentation pattern of the substrates and metabolites.
It can process from multiple vendors: Agilent, Bruker, Sciex, Thermo and Waters, and it is also able to analyze data from different acquisition modes: DDA, DDA, MSE, HDMSE, AIF, AF, Broad band, SWATH, Sonar, etc.
In the cases where the data cannot be used to propose a single structure for the chromatographic peaks found, the system also introduces the Site of Metabolism (SoM) prediction from MetaSite computation (the leader in the metabolism prediction market), that ranks the multiple structural options. Moreover, the user has access to the visual analysis of the enzyme-metabolite interaction CYPs, FMO and AOX proteins, and it can even propose structural modification to overcome the metabolic liability.
- Automatic peak detection
- Structure elucidation
- Comparison with parent
- Metabolite specific fragmentation
- Batch processor:
- Auto-processing of experiment files
- Multiple process batches
- New tool to create WebMetabase Protocol Instances/Batches on sample list import time
- Exporting to excel report
- Markush handling depiction
- Modes of operation:
- Standard
- Standard advanced: user defined mass shift analysis
- GSH: Neutral lost and fragment ions
- Cyanide
- Peptide (up to 4500 amu)
- Signal process:
- Mass Spectrometry, UV, Fluorescence and Radio files
- Direct connection to design tools:
- MetaDesign module available, 32D, MetaSite, Metabolite generation, Automatic validation
- Isotope labeling:
- Stable GSH and cyanide isotope labeling
- Radio isotope labeling
- Enhanced peak quality analysis:
- Area compared to the Blank
- Area compared to the Substrate
- Isotope similarity score
- Improved connection to Waters_connect
- Allows missing zero values in Mol or SDF files
- Tagging of metabolie names based on custom mass shifts
- Custom biotransformations based on formula changes
- Automatic update of metabolite formulas based on selected structures in detail view
- Vendor Neutral: Waters (.raw, .mzML, waters_connect), Thermo (.raw), Sciex (.wiff,.wiff2), Bruker (.d and tsf), Agilent (.d), SLIM (.d)
- Multiple acquisition modes: Waters (MSE, HDMSE, DDA, Sonar, QQQ), Thermo (AIF, DDA, Polarity switching), Sciex (DIA, SWATH acquisition), Bruker (PASEF, TIMSTof, ) and Agilent (AutoMSMS, All Ions)
- User defined mass shift peak selection checks
- Preferred mass list generation (Waters, Thermo, Agilent)
- Possibility to select a UV range for UV chromatogram extraction
- Reduced SMS files size
- Automatic peak detection
- Structure elucidation
- Comparison with parent
- Metabolite specific fragmentation
- Batch processor:
- Multiple process batches
- Tool to create WebMetabase Protocol Instances/Batches on sample list import time
- Visualization in monomers and/or atomic notation
- Monomer Database
- Charge state from isotopic pattern
- Monoisotopic, Most abundant Isotope or average m/z processing methods
- Signal process:
- Mass Spectrometry, UV, Fluorescence and Radio files
- Isotope labeling:
- Radio isotope labeling
- Enhanced peak quality analysis:
- Area compared to the Blank
- Area compared to the Substrate
- Isotope similarity score
- Improved connection to Waters_connect
- Allows missing zero values in Mol or SDF files
- Read structures as SDF or FASTA format
- Process Oligo monomers having a cyclic phosphoamidate group instead of the usual phosphodiester
- Better support for oligopeptides
- Tagging of metabolie names based on custom mass shifts
- Custom biotransformations based on formula changes
- Automatic update of metabolite formulas based on selected structures in detail view
- Vendor Neutral: Waters (.raw, .mzML, waters_connect), Thermo (.raw), Sciex (.wiff,.wiff2), Bruker (.d and tsf), Agilent (.d), SLIM (.d)
- Multiple acquisition modes: Waters (MSE, HDMSE, DDA, Sonar, QQQ), Thermo (AIF, DDA, Polarity switching), Sciex (DIA, SWATH acquisition), Bruker (PASEF, TIMSTof, ) and Agilent (AutoMSMS, All Ions)
- User defined mass shift peak selection checks
- Improved charge assignment, peak detection and speed for Macromolecules
- Added options to expand all monomers
MassMetaSite Training documents
- MassMetaSite: Getting started:
- Tutorial_MMS_01. Metabolite Identification for Human Liver Microsome Incubation of Verapamil and Data Dependent scan acquisition using Thermo FT Orbitrap
- Tutorial_MMS_02. Effect of UV Acquisition: Metabolite Identification for Hepatocytes Incubation of Ebastine and Data Dependent scan acquisition using Thermo FT Orbitrap
- Tutorial_MMS_03. Effect of the filtering threshold settings: Metabolite Identification for Human Liver Microsomes incubation of Dextromethorphan in MSe acquisition
- Batch Process:
- Tutorial_MMS_04. MassMetaSite Batch processing: soft spot batch for h compound. Sample List
- Tutorial_MMS_05. MassMetaSite Batch processing: soft spot batch for h compound, directly in the application without Sample List
- Tutorial_MMS_06. UNIFI connection. Running samples from a UNIFI server using Ion Mobility data
- Reactive Metabolite mode
- Tutorial_MMS_07: GSH trapping experiment
- Tutorial_MMS_08: Radio labelled experiments
- GSH trapping.
- Cyanide trapping
- Macromolecule:
- Single Molecule process:
- Tutorial_MMS_09: Analysis of a linear peptide with natural amino acids: the calcitonin case
- Tutorial_MMS_10: Analysis of a cyclic peptide with natural amino acids: the somatostatin case
- Tutorial_MMS_11: Analysis of a cyclic peptide with natural amino acids: the Somatostatin derivative case
- Tutorial_MMS_14: Analysis of an antisense oligonucleotide
- Batch process:
- Tutorial_MMS_12: Analysis of a family of compounds
- Tutorial_MMS_13: Analysis of a time series for Somatostatin
- Single Molecule process:
Pharma – Data Analysis – Met ID
Articles:
- Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications
- October 2020. Goracci L, Desantis J, Valeri A, Castellani B, Eleuteri M, Cruciani G.J
- Metabolite Identification Using An Ion Mobility-Enhanced Data-Independent Acquisition Strategy and Automated Data Processing. Rapid Commun Mass Spectrom
- June 2020. Radchenko T; Kochansky CJ; Cancilla M; Wrona MD; Mortishire-Smith RJ; Kirk J; Murray G; Fontaine F; Zamora I
- Development, optimization and implementation of a centralized metabolic soft spot assay
- April 2017. Paiva AA; Klakouski C; Li S; Johnson BM; Shu YZ; Josephs J; Zvyaga T; Zamora I; Shou WZ
- Metabolism study and biological evaluation of bosentan derivatives
- October 2016. Lepri S, Goracci L, Valeri A, Cruciani G.
- Software-aided structural elucidation in drug discovery
- November 2015. Ahlqvist M; Leandersson C; Hayes MA; Zamora I; Thompson RA
- High-throughput, computer assisted, specific MetID. A revolution for drug discovery
- Spring 2013. Zamora I; Fontaine F; Serra B; Plasencia G
- Software automation tools for increased throughput metabolic soft-spot identification in early drug discovery
- May 2013. Zelesky V; Schneider R; Janiszewski J; Zamora I; Ferguson J; Troutman M
- Update on hydrocodone metabolites in rats and dogs aided with a semi-automatic software for metabolite identification MassMetaSite
- May 2013. Li AC; Chovan JP; Yu E; Zamora I
- Enhanced metabolite identification with MS(E) and a semi-automated software for structural elucidation
- November 2010. Bonn B; Leandersson C; Fontaine F; Zamora I
Posters:
- Kinetic analysis during the metabolite identification process
- 05 June 2016. 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX (United States of America)
- Development of higher-thoughput metabolic soft spot assay with integrated assessment of Glutathione adduct formation
- 05 June 2016. 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX (United States of America)
Videos:
- PROTAC Metabolite Identification
- Practical Applications for Drug Discovery 2020 Webinar. Ismael Zamora
- Automation of Metabolite Identification
- Practical Applications for Drug Discovery 2020 Webinar. Ismael Zamora
- Spatial Localization and identification of Drug and Metabolites
- Practical Applications for Drug Discovery 2020 Webinar. Sara Tortorella, Giulia Coliva
Pharma – Data Analysis – Reactive Metabolite Screening
Articles:
- Post-acquisition analysis of untargeted accurate mass quadrupole time-of-flight MS(E) data for multiple collision-induced neutral losses and fragment ions of glutathione conjugates
- December 2014. Brink A; Fontaine F; Marschmann M; Steinhuber B; Cece EN; Zamora I; Pähler A
- Enhancing throughput of glutathione adduct formation studies and structural identification using a software-assisted workflow based on High Resolution Mass Spectrometry (HRMS) data
- October 2016. E.N. Cece-Esencan, F. Fontaine, G. Plasencia, M. Teppner, A. Brink, A. Pahler, I. Zamora.
- Software-aided cytochrome P450 reaction phenotyping and kinetic analysis in early drug discovery
- January 2016. Cece-Esencan EN; Fontaine F; Plasencia G; Teppner M; Brink A; Pähler A; Zamora I
Biopharma – Data Analysis – Peptide Metabolite Identification
Articles:
- WebMetabase: cleavage sites analysis tool for natural and unnatural substrates from diverse data source
- February 2019. Radchenko T; Fontaine F; Morettoni L; Zamora I
- Software-aided approach to investigate peptide structure and metabolic susceptibility of amide bonds in peptide drugs based on high resolution mass spectrometry
- November 2017. Radchenko T; Brink A; Siegrist Y; Kochansky C; Bateman A; Fontaine F; Morettoni L; Zamora I
Posters:
- Software assisted analysis for Peptide Catabolism
- Institute for Research in Biomedicine (IRB Barcelona) 35 EPS European Peptide Symposium, Dublin (Ireland) … August 2018
- Peptide catabolite identification using HDMSE Data and MassMetaSite processing
- 66th ASMS Conference on Mass Spectrometry and Allied Topics, San Diego (United States of America) … 06 June 2018
- Peptide metabolism: High resolution mass Spectrometry tool to investigate peptide structure and amine bond metabolic susceptibility
- American Peptide Symposium, Whistler (Canada)… 17 June 2017
- Peptide metabolism: Identification of Metabolite structures of GLP-1 receptor agonists in different in-vitro systems using high resolution mass spectrometry
- 64th ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX (United States of America) … 05 June 2016
Videos:
- Metabolite ID For Peptides Made Simple
- Practical Applications for Drug Discovery 2020 Webinar. Tatiana Radchenko
- Proprietary Peptide Visualization Within MassMetaSite
- Practical Applications for Drug Discovery 2020 Webinar. Tatiana Radchenko
Biopharma – Data Analysis – Peptide Degradation
Posters:
- Automatization of structural elucidation workflow for detecting degradation impurities in Peptides
- February 2020. Elisabeth Ortega-Carrasco, Blanca Serra, Ismael Zamora
- High resolution Mass Spectrometry with automated data analysis to support structural elucidation of degradation impurities of small peptides
- AAPS 2019 PHARMSCI 360, San Antonio (United States of America)… 03 November, 2019
