Posted by: tvasailor | May 24, 2012

Overview “Known Unknowns”

New:  ASMS 2020 Reboot Workshop:  Library Searching Presentation

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Systematic Process for the Identification of “Known Unknowns” in Commercial Products by GC-MS and LC-MS

Note: Details on other subjects are found in “My Topics” tab under sailboat picture above or on the sidebar links to the right..

Introduction:  In the last 34 years, we have developed a systematic process for the identification of “known unknowns” by GC-MS and LC-MS in commercial products.  We define “known unknowns” as non-targeted species which are known in the chemical literature or mass spectrometry reference databases, but unknown to the investigator.  The process is shown in the following simplified flowchart:

flowchart3

This process is described in detail in the February 2013 copy of LCGC, “MS-The Practical Art.”  The article is entitled:  “Identifying “Known Unknowns” in Commercial Products by Mass Spectrometry.”  A copy with associated ads is shown below:

LCGC PDF with Advertisements

or the direct link to the Chromatography Online Website:

LCGC Article On-Line Link

which can be printed using the instructions in this link.  The article originated from work presented at Pittcon in 2012.

NIST Search of EI and CID Spectra:  The initial step in our process utilizes computer searches of EI (GC-MS) or CID (LC-MS) spectra against reference databases using the NIST MS search.  The computer EI searches normally work better than CID ones, but the latter are still very useful.  We employ both purchased, in-house, and internet databases:

types_of_databases_searches
We use the NIST and Wiley commercial databases, but there are many other specialty databases that others might find useful.

The NIST search interfaces easily with a wide variety of manufacturers’ data processing and structural drawing programs:

nist_search

“Spectra-Less” Database Searching:  If the NIST search is not successful, then accurate mass data is used to obtain a molecular formula (MF), a monoisotopic mass, or an average molecular weight.  This data is used to search very large databases such as the CAS Registry (>70 million entries) or ChemSpider (>28 million entries) via web interfaces.  We define them as “spectra-less” databases because they contain no computer-searchable mass spectral data.  We had originally used this approach to search the TSCA database or our Eastman Chemical plant material listing.

The candidate structures from the CAS Registry or ChemSpider searches are prioritized by either the number of associated references or key words.  Other ancillary information such as mass spectral fragments in EI or CID spectra; isotopic abundances, UV spectra; types of ion adductsCI data; number of exchangeable protons;  etc. are used to narrow the list to one structure.  This website has many screenshots (SciFinder1, SciFinder2, ChemSpider) that illustrate these approaches with many examples.

Model EI and CID Spectra from NIST Structure Search:  The NIST MS Search program ranks model compounds employing structural searching of both our commercial and in-house databases.  This is particularly valuable for finding model compounds for a proposed structure found in searches of “spectra-less” databases such as the CAS Registry and ChemSpider.

As noted in the table above, there are ~800,000 structures associated with the EI spectra and 100,000 structures with CID mass spectra in our computer-searchable databases.  We use the NIST MS Interpreter  program to automatically correlate fragment ions in the EI and CID spectra with the component’s substructure.

“No Results” from Process:  There will be non-targeted species in the sample which are “unknown unknowns”, those not found in any reference libraries or “spectra-less” databases.  A few thoughts on their identification are discussed in another section.

Future Improvements Needed:  The approach works well for the majority of our samples which are fairly simple and contain components with molecular weights <500 daltons.  On the other hand, improvements are needed for complex samples and components with molecular weights >500 daltons.

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Posted by: tvasailor | June 29, 2020

Holder 20 For Sale

[Sold to Sailor at Concord Yacht Club, 7/1/2020 in Knoxville, TN]

I had planned on using this boat as my main sailboat for racing.  However, I found another Holder 20.  Thus I would like to sell this one for a very good price.  I am not trying to recoup all my expenses.

$2,300.00

Nevertheless, the boat is in very good racing shape and would only some part of the deck painted and slightly sanded.

I have included some pictures and bills for some but not all of the work at the following link:

Pictures of Boat and Some Bills
Note:  Used Slideshow mode in Shutterfly for easy viewing

List:

-long cockpit Holder 20 (much better than short cone for racing!)
-new Genesis Sobstad Lightwave main new ($1,293.00)
-new Genesis  Sobstad Lightwave Headsail new ($1,038.00)
-jib by Slo new
-zippered Sobstad bags for sail storage
-spinnaker bag to hang down below to launch spinnaker from cockpit
-three winches on top of cabin, two in cockpit
-cockpit tent
-new halyards and main sheet
-new hardware blocks for traveler
-epoxy racing bottom by Waters $2,555.00-
-hardware exit plates in mast for internal halyards, deck organizer plate and associated blocks on mast step, deck blocks, spinnaker crane, etc. by Todd Weir $1423.00
-deck reinforced by Todd Weir in mass step area
-stern of boat stiffened on the inside by Todd Weir
-trailer
-spinnaker with quick disconnect for sheets
-tapered spinnaker sheets with quick disconnects
-twing lines with attached snatch blocks
-through deck twing lines exiting to fairleads/cam cleats in cockpit for easy access and no deck clutter
-trailer with spare tire and poles for guiding boat onto trailer
-backstay flicker on top of mast
-ratchet blocks on stern for spinnaker

 

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I had the opportunity to present at the ASMS Workshop:  “Compound Identification by Mass Spectral Searching, June 3, 2020.  Unfortunately, there were serious problems with my connection and I was unable to present the information.

Here is a link if you are interested.

ASMS Workshop Presentation

asms_reboot

 

Posted by: tvasailor | February 8, 2019

Bridge Game Links

I have had a really good time playing duplicate bridge with many different people in Kingsport, Abingdon, and Johnson City.

The clubs often offer basic “learn to play (free)” courses led by Jan Bruce and Vivian McIntire.  During the recent “Corona Virus” break, the Abingdon Bridge Club has been hosting  “intermediate” bridge lesson series via Zoom that include all the conventions to facilitate an effective 2 over 1 approach to bridge bidding.

see the Abingdon Facebook site

The internet is also a great “bridge teacher.”

I wanted to share some links that I have found very useful for learning to bid and play.

For standard bridge, the following “cheat” sheet summarizes all basic rules:

Basic Bridge Bidding

The New York City Learn Bridge has great more advanced bidding protocols and tactics for playing hands.

I really like YouTube videos!

New York City Learn Bridge

Phillip Holland does great YouTubes demonstrating bidding and playing hands:

Australian Phillip Holland WebSite

Here is an example of one of his YouTube Videos:

Phillip Holland YouTube Example

Posted by: tvasailor | September 15, 2018

Tesla Cars

I had read the biography of Elon Musk, and decided I couldn’t afford a ride on Space-X.   Therefore, the only logical decision was to instead buy a used Tesla.

I bought a 2014 certified preowned Model S85 in July 2018.  Tried to keep price to minimum by not selecting one with a panoramic roof, air-suspension, and dual wheel drive.

Used Tesla Site

The only problem that I have encountered is that I can’t wipe that silly grin off my face everytime I drive it!  The smooth, quick acceleration is addictive.

Added some information about the car in the following PDF that I put together for a local car show at Allandale.

Model S Tesla Information

Nikola Model S

I added a personalized as a result of a gift a colleague gave me when I retired from Eastman.  The following is a snapshot of my Facebook post:

massman_facebook

 

Posted by: tvasailor | August 3, 2015

Useful Tips for 1D and 2D NMR Experiments

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NMR

I have primarily done mass spectrometry during my career, but also utilize NMR data in conjunction with mass spectrometry data to identify components.  Often even relatively complex mixtures can be characterized by 1D and 2D NMR data utilizing complimentary information obtained by either LC-MS or GC-MS analyses.

Laura Adduci shared with me a very useful NMR presentation of tips, tricks, and techniques.  Laura currently works in our NMR laboratory at Eastman Chemical Co., but prepared the presentation while attending UNC-Chapel Hill.

NMR at UNC:  Tips, Tricks, and Techniques

We also utilize both carbon and proton NMR for quantitative analyses.  It is a very powerful approach because standards are not required to calibrate the instrument response.  All that is required is that the component or components of interest be correctly identified.  I have included three links below that I have found very useful for quantitative NMR analyses:

Practical Guide for Quantitative 1D NMR Integration

Practical Aspects of Quantitative NMR Experiments 

Quantitative 1H NMR

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Posted by: tvasailor | March 17, 2015

Archives of Old Articles and Mass Spec Documentation

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raiders_of_the_lost_archive_450
ASMS History Site:  The American Society for Mass Spectrometry has a great site managed by ASMS member/archivist, Michael Grayson.

ASMS History Site

CHF HIstory Site:   Also, great information at the Chemical Heritage Foundation site.

CHF History Site

BMSS History Site:  A new history site for the British Mass Spectrometry Society site.

BMSS History Site

Historical Documents from My Archives:  I found many mass spec artifacts when cleaning out my office in anticipation of retirement in early 2016.  My wife warned me their wasn’t unlimited room in our house or on our sailboat for lots of things.  Thus, I began to sort through and discard things in my office at Eastman and post ones of general interest on my website.

Finnigan Corporation:  A lot of my early career was greatly influenced by GC-MS software (INCOS) and hardware (chemical ionization) from the Finnigan Corporation.  Thus, many of the items on this archive page originated from Finnigan.

I was love stricken in my first encounter with our Finnigan 4000 series instrument and my love affair continued with the TSQ, DSQ, and ISQ instruments.  But possibly the first love was the best.  The Finnigan 4000 was a phenomenal piece of technology, software and hardware, for her time.  We routinely ran the instrument 24/7 using automated acquisition and automated data processing for both qualitative and quantitative analyses.

finnigan_4000

I found several articles about Robert E. Finnigan on the internet that I found interesting inlcuding a short biography and a long interview.

Robert Finnigan short biography
Robert Finnigan long inverview

Finnigan Cookbook, 1979:  This is the Finnigan Cookbook given to me by Bill Tindall, a retiree from Eastman Chemical Company.  It had the following documentation on the front page:

“Marcie got the recipe and passed it to Mark Weiss of Finnigan-INCOS.  Mark Weiss compiled it into his now famous cookbook using what is now considered the first word process software which was written by Joel at INCOS.  The cookbook was printed from the Stanford computer Christmas day in 1979, copied at Finnigan during the dark of night and distributed to its contributors who were acknowledged only by their street names.  For all that its not a bad recipe.”

I made only a few changes when scanning the document.  I did character recognition and added title pages between sections because the handwritten ones could not be scanned.

Finnigan Spectra Vol 6 No 1 (1976):  I always enjoyed the early Finnigan Newsletters.  This newsletter contained the following very useful article which we utilized the work of Hunt on our Finnigan 4000/4500 in 1979 in the analyses of photographic chemicals for Kodak:

-Selective Reagents for Chemical Ionization Mass Spectrometry, Don Hunt, University of Virginia
-Application of Gas Chromatography-Chemical Ionization Mass Spectrometry to the Analysis of Microquantities of Choline and Its Esters, Israel Hanin, University of Pittsburgh School of Medicine

Finnigan Spectra Vol 2 No 1 1972:  Another old Finnigan Newsletter containing articles with articles by M. S. Story and R. E. Finnigan and other things.

Chemical Ionization Mass Spectrometry, E. J. Bonelli, M. S. Story
Analysis of a Kraft Paper Mill Effluent by Electron Impact and Chemical Ionization GC/MS, J. B. Knight, E. J. Bonelli, and R. E. Finnigan
GC/MS of Chlorinated Dioxins, E. J. Bonelli
Dateline:  Finnigan acquires Quanta/Metrix

Finnigan Spectra Vol 12 No 1, Spring 1989:  A collection of early LC-MS articles in a Finnigan magazine.

Letter to the Reader, Richard M. Caprioli
Continuous Flow Fab, Richard M. Caprioli
Capillary Zone Electrophoresis/Mass Spectrometry:  An Alternative to LC/MS?, Richard D. Smith, Charles J. Barinaga, and Harold R Udsetb
Supercritical Fluid Chromatogrpahy/Mass SPectrometry (SFC/MS), D. E. Games, A. J. Berry, S. Y. Hughes, S. Mahatheeranont, I. C. Mylchrest, J. R. Perkins, E. D. Ramsey, and S. Pleasance
Thermospray LC/MS:  Effect of Experimental Parameters on Spectra and Sensitivity, Patrick J. Rudewicz
Perspectives on the Moving Belt LC/MS Interface, J. van der Greef, W. M. A. Niessen, and U. R. Tjaden

Finnigan Spectra Vol 9 No 1 Spring 1983:  Another collection of early LC-MS articles, listed Finnigan thermospray interface.  The Thermospray interface is the first useful interface utilized at Eastman Chemical Company.  We utilized the Vestec interface on our Finnigan 4000/4500 GC-MS.  We tried a moving belt interface on a contract instrument in Boston, but we were not impressed, and thus, never purchased one.

Introduction, D. E. Games, guest editor
Combined Liquid Chromatography/Mass Spectrometry (LC/MS), D. E. Games
The Moving Belt as an Interface for HPLC/MS-P. Vouros, B. L. Karger
First Steps in LC/MS with Simple Interfaces for the Finnigan MAT 44-N. Evans
Experiments with the Coupling of a Jasco Micro LC to a Finnigan MAT 3300 Quadrupole Mass Spectrometer, A. P. Bruins, B. F. H Drenth
Thermospray LC/MS:  Supplement of Substitute for Existing Techniques, W. H. McFadden

Finnigan Application Report Number AR8020, 1979?:  We found negative ion LC-MS to be really useful for Thermospray and later electrospray analyses.  We did some negative ion GC-MS, but not as universally useful.  Here is an early report on negative ion MS from Finnigan:

Biomedical Applications of Negative Ion Chemical Ionization Mass Spectrometry, John R. B. Slayback and M. N. Kan, Finnigan Corporation

Finnigan Application Report No 47, 1982?:  We did a lot of direct chemical ionization on both our Finnigan 4000/4500, Finnigan 700/7000, and even our Autospec.  Worked reasonably well before the days of electrospray.  We normally would isolate compounds by preparative TLC or flash chromatography.

DCI-Direct Chemical Ionization or Desorption Chemical Ionization, A Powerful Soft Ionization Technique in Mass Spectrometry, U. Rapp, G. Meyerhoff, and G. Dielmann

Finnigan Technical Report No TR8027:  I loved my first GC-MS instrument, a Finnigan 4000 and its associated Data General computer, analytical-digital interface, jet separator, chemical ionization source, oscillope for tuning, library search software, etc.  Here is the information needed to optimizie the INCOS data system.

Optimization of Acquisition Parameters for the INCOS Data System, Rhilip L. Warren, John R. B. Slayback, Carl R. Phillips

Finnigan TSQ70-We had a Finnigan TSQ-70 and two SSQ-70’s.  We really enjoyed all three instruments doing a lot of chemical ionization work, Vestec thermospray interface, Vestec particle bean interface, fast atom bombardment interface, and direct chemical ionization.  Here is a picture that Steve Lammert shared with me recently.  It is of the  TSQ 70 development team photo ca. 1985.

tsq70

Direct Liquid Introduction (DLI) LC-MS Interface, 1984:  Jack Henion came to our lab to install the DLI interface.  He was a consultant for Kodak in Rochester.  Many people referred to it as “Pray and Spray” because always plugging.  Here is some documentation and data I retained even the parts listing for the various laser drilled holes.  We only used a very short time before transitioning to the Thermospray interface.

Vestec Particle Beam Interface Brochure:  We used this for several years in both EI and CI modes on our Finnigan TSQ-700.  It actually worked well, but the sensitivity was very poor compared to current electrospray interfaces.  Nevertheless, one could get good EI spectra for library searching and addition to our computer searchable Eastman Corporate Database.

Additional Particle Beam Information:  I have included some additional data on the Vestec interface, the Hewlett-Packard demo, the Extrel Thermabeam interface, and the Particle Beam/FAB interface custom-built by Marvin Vestal for our VG-70 MS,  etc.

Kodak Laboratory Chemicals Bulletin Vol 55, No 3, 1984:  When I was in graduate school in the late 70’s, we ordered specialty chemicals from Kodak.  They supplied many in that era, but nothing to compare to the large list of chemicals from Aldrich.  Here is a bulleting talking about “The Chemistry of the Diketene-Acetone Adduct” by Robert J. Clemens, CAS No. 5394-63-8, 2,2,6-trimethyl-4H-1,3-dioxin-4-one.

MS9 Design Lectures, AEI, Associated Electrical Industries Limited:  I think we had a MS9 in the Kodak Rochester laboratories.  We did have a CEC 21-110B mass spectroemeter in Research at Eastman Chemical.  We used the instrument at Eastman to characterize TLC fractions, prepared samples, and even components trapped off a GC/TCD system.  Thus the beginnings of GC-MS!

Finnigan 1015 GC-MS:  We had one of these systems at Eastman.  Bob Finnigan would always ask me about it every year when I attended ASMS in the mid 80’s.  The picture below was from the Heritage article written by David C. Brock.

finnigan 1015 picture

INCOS 50:  We had one of these systems.  It always looked to me as if someone had made the manifold for the system produced from a “glass sewer pipe.”  Probably the best part of the instrument was the INCOS library search software:

S. Sokolow, J. Karnofsky, P. Gustafson, The Finnigan Library Search Program, Finnigan Application Report 2, San Jose, CA (1978).

A good friend of mine supplied me a copy of the report.

Here is a link to an ACS advertisement for the instrument featuring Bob Finnigan.

incos 50

British Mass Spectrometry History:  One of my wife’s British relatives, Winifred Hall, was a early scientist in mass spectrometry at Shell.  When we went to visit her, she introduced me to several people in the mass spectrometry industry including Robert Craig.  Robert was an early founder of VG.

This was actually before my career in mass spectrometrist at Eastman Kodak.  At the time, I was attending the University of Georgia as a graduate student in chemistry, but our school did not have a working mass spectrometer.  It had been “hit” by lightening and no one knew how to repair the beast!

I found a lot of history of the British mass spectrometry community on the British Mass Spectrometry website that is very interesting.

Mike Morris – 50 years of British MS

BMSS 50th poster by ASMS

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Posted by: tvasailor | July 11, 2014

Accurate Mass User Libraries in NIST14 Release

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Users can now add accurate mass EI and MS/MS to their libraries.  This is an updated feature distributed with the recent NIST 14 library and Search software release.  A brochure from a distributor is shown below and also another link to “What’s New”:

NIST Brochure

“What’s New NIST14”

I have shown some examples of accurate mass EI and MS/MS spectra in the link below.  The data was obtained on a Waters GCT and processed in MassLynx.

Examples User Accurate Mass EI and MS/MS Spectra in NIST14 Software

The next link details information from David Sparkman for utilizing FreeStyle.  This application is supplied by ThermoFisher with their Orbitrap (Q Exactive).  It is a stand-alone data processing application that will transfer accurate mass EI data to the NIST search software.  The Qual Browser software within Xcalibur will not export accurate mass data to the NIST search.

Detailed information for Orbitrap EI data Export to NIST

The last link contains abbreviated instructions written by J. Little for exporting EI Orbitrap data to NIST using FreeStyle:

Abbreviated information for Orbitrap EI Data to NIST

acc mass

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Posted by: tvasailor | June 20, 2014

University of Georgia Graduate Work 1978

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My thesis at the University of Georgia was supported by federal grant money to develop solar energy.  It was based on the “Evaluation of Heterogenous Photosensitizers.”  The solid state sensitizers were used to store energy by the conversion of  norbornadiene to quadricyclane.  The quadricyclane can then be converted quantitatively back to norbornadiene to recover the energy in the form of heat.

Thesis Link

solar_energy

I have also included my graduate Seminar on “Brevicomin:  Structure and Synthesis of a Novel Natural Product.”

Brevicomin Link

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Posted by: tvasailor | July 5, 2013

File Conversions and Data Intechange

File Conversions and Data Interchange

Eastman supported the early efforts in netCDF/Andi.  It has always been very important for our users to be able to convert files from one vendor’s format to another.  Often one software package will have capabilities that another doesn’t possess or someone might only have training in one software package and not another.  We served on ASTM committees and also we required vendors to supply the format as part of instrument purchases.

These capabilites have been critical to our operations since those early days and they are still employed daily!  Our early work was discussed briefly in one of the Andi Newsletters in 1995.

We currently use file conversions daily.  We primarily convert files obtained on our Thermo DSQ GC-MS systems to netCDF format using Thermo’s  File Converter program.

thermo_file_converter

The resulting netCDF files are then converted with Water’s DataBridge program for processing with Water’s MassLynx software package.

waters_file_converter

In addition, we use MassTransit which is a legacy product still distributed by Scientific Instrument Services Company.  It is used primarily for converting files to and from our Agilent GC-MSD instruments to other vendor formats.

mass_transit

Scientific Instrument services also sells another translator package called GC/MS File Translator, but we have not used that program.

Dr. Philip Winig (see his comments below) sent me a note about OpenChrom software.  It is open source software for chromatography and mass spectrometry based on the Eclipse Rich Client Platform (RCP). Its focus is to handle mass spectrometry systems (e.g. GC/MS, LC/MS, Py-GC/MS, HPLC-MS) data files natively, but also performs files conversions.  I haven’t had the opportunity to evaluate the software.

Posted by: tvasailor | December 30, 2012

“Known Unknown” Future Improvements Needed

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Our approach works well for the majority of our samples which are fairly simple and contain components with molecular weights <500 daltons.  On the other hand, improvements are needed for complex samples and components with molecular weights >500 daltons.  I have discussed some of my thoughts and opinions below and a good review of small molecule identification was recently published.

1.  CAS Registry/SciFinder:  The major improvement needed in SciFinder is the addition to search by monoisotopic mass within a specified m/z error window.  This would be especially useful for higher molecular weight components, but could be used effectively for all components eliminating the need for any subjective decisions in specifiying the elements searched, numbers of double bond equivalents, numbers of elements, etc. in the determination of a molecular formula.  The resulting structures from the monoisotopic searches could be returned to the manufacturers’ software and further ranked/sorted by their isotopic fidelity and mass error.

Recently, CAS did add the ability to search by average molecular weight in SciFinder.  This capability was only previously available in STN Express.  This is useful, but the monoisotopic mass can be determined with much better precision and accuracy than the average molecular weight.  At lower m/z values too many candidates are recovered due to the very large number of components in the CAS Registry between 300-500 daltons and the large measurement error.

ChemSpider has an applications program interface (API) which can be used by manufacturers to query the ChemSpider database and return results to their interfaces for further processing/displaying.  A similar type approach would be very useful for the CAS Registry.  The Registry does currently allow one to manually export a reasonable number mol files (structural connection tables) in an SDF file format.  It would be very desirable to also included other fields in the SDF file such as the number of associated references.

Other needed improvements (limitations) are found on page 12 of a prepress article found on this website.

2.  Chemspider:  There are many duplicate structures in ChemSpider for the same compound.  CAS Registry does a better job of listing a unique structure for each record.  Several other suggestions for ChemSpider are found on page 8 of a prepress article.

3.  In-Silico Fragmentation:  Many programs exist for the in-silico fragmentation of structures including MS Interpreter (NIST), MetFrag, Molecular Structure Correlator (Agilent), MathSpec (D. Sweeney), and Fragmentation Prediction Tool in PeakView Software (AB Sciex).  Much more needs to be done in this area to improve the reliability of ranking candidate structures by comparison of in-silico spectra to acquired CID spectra.  A section in a review article discusses the current state of in silico work.

4.  Automated Processing and Reporting:  Manufacturers are improving their automatic processing and reporting for LC-MS and GC-MS, but we still spend an unacceptable amount of time hand-annotating chromatograms for customers.  Much of this could be avoided if manufacturers would further improve their software.

It would be very powerful if both ChemSpider and CAS Registry used application program interfaces to obtain structures and associated numbers of references which would be returned to the manufacturers’ software programs.  They could then be ranked by individual scores considering the number of associated references, isotopic fidelity, mass accuracy, isotopic spacing, elemental composition from fragmentation data, in-silico fragmentation, commercially availability, etc.  Then an overall score could be assigned by weighting these individual scores to allow sorting of the candidate structures.

Someday..

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