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Top Six Reasons Upgrading Your Small Molecule Structural Elucidation Approach May Be in Order

Team TFS
Team TFS
elucidationWhether the mass spectrometry-based approach you use today is tedious and time consuming, doesn’t deliver the confident results you need or you are running low on talent with technical competency, it might be time to re-evaluate your approach to small molecule identification and characterization so you are better equipped now and in the future.  Interpreting the mass spectra of unknown compounds remains challenging and is a frequent bottleneck in many fields, including untargeted metabolomics research, food safety testing, industrial and environmental research, as well as drug development.

Here are six reasons why you might want to access the latest technological advancements along with new, intelligence-driven acquisition and automated data analysis approaches enabled by the newest Thermo Scientific™ Orbitrap™ Tribrid™  mass spectrometers.

#1 MS2 data may no longer be sufficient, and new data acquisition and analysis solutions to utilize MSn efficiently are now available

Investing in your next mass spectrometer isn’t an easy decision. You need flexibility to accommodate complex and changing samples; including matrices, analytes of interest and methodology approaches. No matter if you support others or conduct your own research, your lab’s mission is ever changing.  Selecting an instrument which serves you today and tomorrow will be key. An essential tool should be equipped with hardware and mass analyzers which provide superior analytical performance AND a variety of detection mechanisms for when MS2 may not be sufficient; particularly when identifying unknown small molecules. Investigating new solutions like the Thermo Scientific™ Orbitrap ID-X™ Tribrid™ mass spectrometer, designed specifically to improve small molecule characterization and identification may be an option.

While a significant portion of all acquired LC/MS fragmentation studies currently remain at the MS/MS level, the lack of standardized mass spectral libraries and the large number of unidentified metabolites continue to limit overall progress in research areas such as metabolomics. “The bottleneck of compound identification is beginning to be overcome” says Dr. Robert Mistrik, CEO & Founder of HighChem in a recent talk entitled “New Generation of Software Tools for the Identification of Compounds.” The ability to use information-rich MSn fragments to provide in-depth structural knowledge of compounds for high confidence identification and structural elucidation along with streamlined data analysis approaches to accelerate identifying more unknowns is now a reality.

#2 Your current data acquisition methodology is time consuming

While some labs continue to develop homebrew approaches or leverage inexpensive labor (i.e. graduate students), why not utilize off-the-shelf supported solutions? Access fully automated iterative exclusion and inclusion lists to obtain fewer redundant/irrelevant data dependent MSn spectra with the Thermo Scientific™ AcquireX intelligent data acquisition approach. Various approaches are available to assist analysts in numerous small molecule research areas from metabolomics to drug development, to food and environmental safety testing.

A variety of AcquireX data acquisition options enable rapid profiling across multiple samples or exhaustive sample interrogation through replicate injections depending on your industry or application needs. Each sequence increases the number of compounds sampled with distinguishable fragmentation spectra for sample and study characterization. Whichever the AcquireX data acquisition methodology approach you select, you can obtain more informative MSn spectra; which significantly increases the number of mass spectral library matches against the open access mzCloud™ online spectral library database.

#3  Your current approach to custom library creation is overwhelming

With the ability to create, curate and manage your libraries within Thermo Scientific™ Mass Frontier™ 8.0 (or greater) spectral interpretation software, comes the power to share your insights across your organization. The Curator feature within Mass Frontier software allows you to use the same tools that curate the mzCloud™ online mass spectral database to create your own high-quality mass spectral libraries. Supplement your knowledge with full precursor and fragment ion structures and formulas, with mass recalibration, adduct detection and annotation, as well as collision energy breakdown curves for your own MSn spectral trees. Your libraries can be easily managed within the Mass Frontier software Data Manager, with this knowledge being shared across your network by the included Server Manager.

#4 You need to confidently assign a structure but you have no spectral library match

Many small-molecule analyses, from metabolism studies and drug analyte analysis, to food and environmental contaminants, rely on the use of the comprehensive spectral libraries to aide in unknown identification.  However, subtle compound transformations (e.g., designer drugs or new impurities) can result in no spectral match. Subsequent searches of extensive online structural libraries can result in hundreds of potential structure matches, but without spectral data, confirming potential structural matches remains a challenge.

The  mzLogic algorithm, included within Thermo Scientific Compound Discoverer 3.0 (or greater) or Mass Frontier version 8.0 (or greater) software, allows comparison of experimental data to the extensive, chemically diverse, fully curated MSn fragment ion information in the mzCloud online library to rank putative structures, increasing efficiency and confidence. You can move from 1000's of candidates and hours of work, to fast automated logical analysis so you can easily maximize both your HRAM MS and MSn data.

See how it works>

#5 You need to enter a new era of metabolome annotation

Metabolite annotation is a current bottleneck in the broad implementation of metabolomics, hindering biological interpretation of results. In LC/MS-based metabolomics, thousands of features from a single sample are routinely detected. However, not all features represent metabolites of biological origin and fragmentation spectra of background ions and degenerate signals detract from metabolite identification efforts.

While high-resolution accurate-mass spectrometry and a variety of homebrew or commercially available data analysis tools continue to evolve, leveraging the Orbitrap ID-X Tribrid mass spectrometer workflow can facilitate the following:

  • Selectively provide comprehensive metabolite coverage using AcquireX

  • Increased confidence in metabolite annotations from searching HCD and/or CID MSn data

  • Use ion tree fragmentation and unique search strategies to classify true unknown compounds

  • Obtaining LC-MSn spectra to provide more complete structure information for isomeric species

During a recent IMSC workshop, Advanced Metabolome Annotation, learning how to combine tested, sophisticated tools can lead to comprehensive metabolome coverage and remove the identification barrier leading to confidence biological interpretation was presented.

#6 You’re a self-prescribed novice

For some, mass spectrometry isn’t easy. With that in mind, our scientists work with scientists like you to build and optimize pre-defined method templates specific to a variety of common applications so you can focus on your science, not on developing methods. We’ve streamlined the mass calibration procedures and made our acquisition methods intelligent to automate more of your data acquisition and improve your success.

 Learn more

 Addressing the "Identity Crisis" in Small Molecule Compound Identification on-demand seminar

Delivering Confidence for Small Molecule Identification White paper

AquireX Intelligent Data Acquisition Technology for Orbitrap Tribrid Mass Spectrometers Smart Note

mzLogic Data Analysis Algorithm Smart Note

Orbitrap ID-X MS for Metabolomics, Lipidomics and Structural Elucidation Grant Application Resource