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ESI-MS: The tool for the identification of chemical species


Speciation analysis is targeting at the detection of unknown elemental species, their identification and/or structural elucidation followed by their quantification. For quantification with respect to the target element, ICP-MS is the perfect tool, providing both unmatched sensitivity and compound independent response. Since the plasma source (often also called atomizer) is destroying all molecular information, species characterization is limited to the retention time provided by the chromatography coupled to the ICP. However species identification by the retention time requires compound standards and is not applicable for unknown species. This gap can be filled by electrospray ionization mass spectrometry (ESI-MS).

In electrospray, a liquid is passing through a nozzle. The plume of droplets is generated by electrically charging the liquid to a very high voltage. The charged liquid in the nozzle becomes unstable as it is forced to hold more and more charge. Soon the liquid reaches a critical point, at which it can hold no more electrical charge and at the tip of the nozzle it blows apart into a cloud of tiny, highly charged droplets.

Fig. 1: Electrospray (nanoSpray) Ion Source in LTQ-FTICR mass spectrometer. photo: Maciej Kotlinski

Exciting potential opportunities are offered by ESI-MS for a soft ionization of metal-containing species and by tandem mass spectrometry (MS/MS) for a precise determination of molecular weight and structural characterization of molecules at trace levels in complex matrices.

Three different approaches are offered in principle by ESI-MS to characterize unknown species:
  • the exact mass of the molecular ion (especially by high-resolution QTOF or FTICR systems) is used to identify the molecular species,
  • isotope patterns can be used to flag the presence of elements and the number of their atoms within the molecule,
  • fragmentation patterns obtained from  MS/MS experiments can be used to obtain information about the structure of the molecule.

The evolution in speciation analysis into the field of metallomics and metabolomics is to a great part due to the advent and spread of electrospray tandem quadrupole and quadrupole time-of-flight (Q-TOF) mass spectrometers in analytical laboratories and their hyphenation with high resolution separation techniques, such as HPLC and CE.

Fig. 2: Publications related to LC-ESI-MS for speciation analysis

However, LC-ESI-MS also has some limitations:
  • Response is compound and matrix dependent (ionization is limited by the constant ion current that is used up by all species present)
  • Sensitivity often is 1-2 orders of magnitude lower than for ICP-MS (depending on the sample introduction system, the matrix load and the analyte species)
  • Quantification requires compound standards
For this reason, speciation analysis often requires a multi-technique approach, where not only more than one technique is used in parallel or sequence but in an integrated approach.

The complementary aspects of LC-ICP-MS and LC-ESI-MS have lead in recent times even to the parallel on-line coupling of both techniques to the same HPLC separation module.

 Tutorial material related to ESI-MS

UCDAVIS CHEMWIKI: Electrospray Ionization Mass Spectrometry
New Objective: What is Electrospray ?

IonSource.com: Interpreting Electrospray Mass Spectra
IonSource.com: Principles of Mass Spectrometry Quantification

JEOL: How resolution is defined
JEOL: Elemental composition calculations and their interpretation
JEOL: Tandem mass spectrometry

Matrix Science: Peptide fragmentation patterns
Matrix Science: Accuracy and Resolution
MS Terms Wiki: Mass Spectrometry Terms and Definitions
SciMedia: Introduction to Mass Spectrometry
SciMedia: Mass Spectrometry Ionization Methods

Separation Science: Dealing with Metal Adduct Ions in Electrospray: Part 1
Separation Science: Dealing with Metal Adduct Ions in Electrospray: Part 2
Separation Science: Adjusting Electrospray Voltage for Optimum Results
Separation Science: The Role of Isotope Peak Intensities Obtained Using MS in Determining an Elemental Composition: Part 1
Separation Science: The Role of Isotope Peak Intensities Obtained Using MS in Determining an Elemental Composition: Part 2
Separation Science: Quantitation in Hyphenated Chromatographic Techniques
Separation Science: Improving Electrospray LODs by Decreasing Column Diameter

Waters: MS Primer
Waters: Common ionization techniques
Waters: Common Background Ions

YouTube: Videos showing the electrospray nebulization process

 Reviews of ESI-MS for speciation analysis (newest first)

S. Indelicato, D. Bongiorno, L. Caraulo, Recent Approaches for Chemical Speciation and Analysis by Electrospray Ionization (ESI) Mass Spectrometry, Front. Chem., 8 (2021) 625945. DOI: 10.3389/fchem.2020.625945

Michael W. Linscheid, Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side-by-side, Mass Spectrom. Rev., 38/2 (2019) 169-186. DOI: 10.1002/mas.21567

T. De Vijlder, D. Valkenborg, F. Lemière, E.P. Romijn, K. Laukens, F. Cuyckens, A tutorial in small molecule identification via electrospray ionization-mass spectrometry: The practical art of structural elucidation, Mass Spectrom. Rev., 37/5 (2018) 607-629. DOI: 10.1002/mas.21551

K. Bierla, S. Godin, R. Lobinski, J. Szpunar, Advances in electrospray mass spectrometry for the selenium speciation: focus on Se-rich yeast, Trends Anal. Chem., 104 (2018) 87-94. DOI: 10.1016/j.trac.2017.10.008

M. Montes-Bayón, M. Sharar, M. Corte-Rodriguez, Trends on (Elemental and Molecular) Mass Spectrometry based strategies for Speciation and Metallomics, Trends Anal. Chem., 104 (2018) 4-10. DOI: 10.1016/j.trac.2017.09.025

Björn Meermann, Michael Sperling, Hyphenated techniques as tools for speciation analysis of metal-based pharmaceuticals: developments and applications, Anal. Bioanal. Chem. 403 (2012) 1501–1522. DOI: 10.1007/s00216-012-5915-9

Dirk Wesenberg, Gerd-Joachim Krauss, Dirk Schaumlöffel, Metallo-thiolomics: Investigation of thiol peptide regulated metal homeostatsis in plants and fungi by liquid chromatography-mass spectrometry, Int. J.Mass Spectrom., 307/1-3 (2011) 46-54. doi: 10.1016/j.ijms.2010.10.026

Marijana Petkovic, Tina Kamceva, FAB, ESI and MALDI Mass Spectrometric methods in the study of metallo-drugs and their biomolecular interactions, Metallomics, 3/6 (2011) 550-565. doi: 10.1039/C0MT00096E

Dirk Schaumlöffel, Andreas Tholey, Recent directions of electrospray mass spectrometry for elemental speciation analysis, Anal. Bioanal. Chem., 400/6 (2011) 1645-1652. doi: 10.1007/s00216-011-4911-9

Robert Jirásko, Michal Holcapek, Structural analysis of organometallic compounds with soft ionization mass spectrometry, Mass Spectrom. Rev., 30/6 (2011) 1013–1036. doi: 10.1002/mas.20309

Miranda J. Keith-Roach, A review of recent trends in electospry ionization-mass spectrometry for the analysis of metal-organic ligand complexes, Anal. Chim. Acta, 678/2 (2010) 140-148. doi: 10.1016/j.aca.2010.08.023

Michaele Scigelova, Alexander Makarov, Advances in bioanalytical LC-MS using the Orbitrap mass analyzer, Bioanalysis, 1/4 (2009) 741-754. doi: 10.4155/bio.09.65

Bente Gammelgaard, Charlotte Gabel-Jensen, Stefan Stürup, Helle Rüsz Hansen, Complementary use of molecular and element-specific mass spectrometry for identification of selenium compounds related to human selenium metabolism, Anal. Bioanal. Chem., 390/7 (2008) 1691-1706. doi: 10.1007/s00216-007-1788-8

Yasumitsu Ogra, Integrated strategies for identification of selenometabolites in animal and plant samples, Anal. Bioanal. Chem., 390/7 (2008) 1685-1689. doi: 10.1007/s00216-007-1796-8

Ryszard Lobinski, Dirk Schaumlöffel, Joanna Szpunar, Review: Mass spectrometry in bioinorganic analytical chemistry, Mass Spectrom. Rev., 25 (2006) 255-289. doi: 10.1002/mas.20069

Andreas Prange, Daniel Proefrock, Application of CE-ICP-MS and CE-ESI-MS in metalloproteomics: challenges, developments, and limitations, Anal. Bioanal. Chem., 383/3 (2005) 372-389. DOI: 10.1007/s00216-005-3420-0

Kevin A. Francesconi, Michael Sperling, Speciation analysis with HPLC-mass spectrometry: time to take stock, Analyst (London), 130/7 (2005) 998-1001. DOI: 10.1039/b504485p

Hubert Chassaigne, Electrospray Methods for Elemental Speciation, in: Rita Cornelis, Joe Caruso, Helen Crews, Klaus Gustav Heumann (eds), Handbook of Elemental Speciation: Techniques and Methodology, John Wiley & Sons, Chichester, 2003, pp. 356-377

Shona McSheehy, Z. Mester, The speciation of natural tissues by electrospray-mass spectrometry. II :Bioinduced ligands and environmental contaminants, Trends Anal. Chem. (Pers. Ed.), 22/5 (2003) 311-326. doi:10.1016/S0165-9936(03)00501-6

Erwin Rosenberg, The potential of organic (electrospray- and atmospheric pressure chemical chemical ionisation) mass spectrometric techniques coupled to liquid-phase separation for speciation analysis, J. Chromatogr. A, 1000 (2003) 841-889. doi:10.1016/S0021-9673(03)00603-4

I.I. Stewart, Electrospray mass spectrometry: a tool for elemental speciation, Spectrochim. Acta, Part B, 54/12 (1999) 1649-1695. doi:10.1016/S0584-8547(99)00110-X

I.I. Stewart, G. Horlick,  Developments in the electrospray mass spectrometry of inorganic species, Trends Anal. Chem. (Pers. Ed.), 15/2 (1996) 80-90. doi:10.1016/0165-9936(96)80764-3

Studies on the instrumentation and instrumental parameters of ESI-MS

Munkhtsetseg Tsednee, Yu-Chen Huang, Yet-Ran Chen, Kuo-Chen Yeh, Identification of metal species by ESI-MS/MS through release of free metals from the corresponding metal-ligand complexes, Sci. Rep., 6 (2016) #26785. doi: 10.1038/srep26785

Ambrose Furey, Merisa Moriarty, Vaishali Bane, Brian Kinsella, Mary Lehane, Ion suppression; A critical review on causes, evaluation, prevention and applications, Talanta, 115 (2013) 104-122. doi: 10.1016/j.talanta.2013.03.048

Lars Konermann, Elias Ahadi, Antony D. Rodriguez, and Siavash Vahidi, Unraveling the Mechanism of Electrospray Ionization, Anal. Chem. 85/1 (2013) 2–9. DOI: 10.1021/ac302789c

Laurent Ouerdane, Juris Meija, Sezgin Bakirdere, Lu Yang, Zoltán Mester, Nonlinear Signal Response in Electrospray Mass Spectrometry: Implications for Quantitation of Arsenobetaine Using Stable Isotope Labeling by Liquid Chromatography and Electrospray Orbitrap Mass Spectrometry, Anal. Chem., 84 (2012) 3958-3964. doi:  10.1021/ac203137n

Alexander Makarov, Michaela Scigelova, Coupling liquid chromatography to Orbitrap mass spectrometry, J. Chromatogr. A, 1217 (2010) 3938–3945. doi:10.1016/j.chroma.2010.02.022

Anas El-Aneed, Aljandro Cohen, Joseph Banoub, Mass Spectrometry, Review of the Basics: Electospray, MALDI, and Commonly Used Mass Analyzers, Appl. Spectrosc. Rev., 44/3 (2009) 210-230. doi: 10.1080/05704920902717872

Paul Kebarle, Udo H. Verkerk, Electrospray: From ions in solution to ions in the gas phase - What we know now, Mass Spectrometry Reviews, 28 (2009) 898– 917. DOI: 10.1002/mas.20247

Jason S. Page, Ryan T. Kelly, Keqi Tang, Richard D. Smith, Ionization and Transmission Efficiency in an Electrospray Ionization-Mass Spectrometry Interface, J. Am. Soc. Mass Spectrom., 18/9 (2007) 1582-1590. doi:10.1016/j.jasms.2007.05.018

Irina Manisali, David D.Y. Chen, Bradley B. Schneider, Electrospray ionization source geometry for mass spectrometry: past, present, and future, Trends Anal. Chem. (Pers. Ed.), 25/3 (2006) 243-256. doi:10.1016/j.trac.2005.07.007

S.H. Hansen, Lars Bendahl, B. Gammelgaard, O. Jons, O. Farver, Hyphenation of CE to ICP-MS and to sheathless electrospray-MS for high sensitivity and selectivity in bioanalysis, Chromatographia, 55/Sup. (2002) S15-S19. doi: 10.1007/BF02493346

Keqi Tang, Yuehe Lin, Dean W. Matson, Taeman Kim, Richard D. Smith, Generation of Multiple Electrosprays Using Microfabricated Emitter Arrays for Improved Mass Spectrometric Sensitivity, Anal. Chem., 73/8 (2001) 1658-1663. doi: 10.1021/ac001191r

Gary A. Schultz, Thomas N. Corso, Simon J. Prosser, Sheng Zhang, A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry, Anal. Chem., 72/17 (2000) 4058-4063. DOI: 10.1021/ac000325y

Andries P. Bruins, Mechanistic aspects of electrospray ionization, J. Chromatogr. A, 794/1-2 (1998) 345-357. doi:10.1016/S0021-9673(97)01110-2

S.A. Shaffer, D.C. Prior, G.A. Anderson, H.R. Udseth, R.D. Smith, An ion funnel interface for improved ion focusing and sensitivity using electrospray ionization mass spectrometry, Anal. Chem., 70/19 (1998) 4111-4119. DOI: 10.1021/ac9802170

Andries P. Bruins, ESI source design and dynamic range considerations, in: R.B. Cole, Electrospray ionization mass spectrometry, John Wiley & Sons, New York, 1997, pp. 107-136.

George R. Agnes, Gary Horlick, Effect of Operating Parameters on Analyte Signals in Elemental Electrospray Mass Spectrometry, Appl. Spectrosc., 49/3 (1995) 324-334. doi: 10.1366/0003702953963463

Andries P. Bruins, Atmospheric-pressure-ionization mass spectrometry. I. Instrumentation and ionization techniques, Trends Anal. Chem. (Pers. Ed.), 13/1    (1994) 37-43. doi:10.1016/0165-9936(94)85057-7

Paul Kebarle, Liang Tang, From ions in solution to ions in the gas phase. The mechanism of electropspray mass spectrometry, Anal. Chem., 65/22 (1993) 972A-985A. doi: 10.1021/ac00070a001

LC-ESI-MS Maintenance and Trouble-Shooting

HPLC Trouble-Shooting
Agilent 1100 Series LC and LC/MS Maintenance Videos (only for registered users)
Mass Spec Source: Mass spectrometer source cleaning
Georgia Institute of Technology: Mass Spectrometry Troubleshooting guide

Separation Science: MS Solutions: Tech Tip: Adjusing electrosptay voltage for optimum results
Waters Support Library
Waters: Controling Contamination in UltraPerformance LC®/MS and HPLC/MS Systems
Waters: Common Background Ions
Common Mass Spectrometry Contaminants and their Sources

EVISA Database system

Journals Database: Journals related to Liquid Chromatography
Journals Database: Journals related to Mass Spectrometry
Company Database: Professional Organizations relelated to Chromatography
Company Database: Professional Organizations related to Mass Spectrometry
Company Database: Manufacturers providing ESI-MS systems
Instrument Database: ESI-MS systems
 Instrument Database: HPLC Autosampler
 Instrument Database: HPLC pumps

EVISA link pages

Resources related to analytical sciences
Resources related to mass spectrometry
Resources related to Chromatography
Resources related to quality assurance/quality control

 Useful tools for MS

Molecular Weight Calculator
Isotope Distribution Calculator and Mass Spec Plotter (online)
MS tools: free software dedicated to MS
SIS: Mass spectrum generator

Other resources

i-mass: Tutorials, Tools, and News related to Mass Spectrometry
Scientific Instrument Services: Mass Spec Tips
Scientific Instrument Services: Exact masses and isotope abundances
NIST WebBook:  a library of spectra
Chromatography Forum (Discussion group)
SeparationsNow: Wiley thematic web portal dedicated to chromatographyl
SpectroscopyNow: BasePeak (Wiley thematic web portal dedicated to mass spectrometry)
Wikipedia:WikiProject Mass spectrometry
The LC/MS Homepage
Shula Levin's Homepage of HPLC and LC-MS
Shimadzu: Fundamental LCMS

EVISA News related to ESI-MS

August 8, 2008: Arsenolipids in Fish Oil
March 16, 2008: New selenium-containing proteins identified in selenium-rich yeast
August 16, 2006: Toxic antimony species found in beverages stored in PET containers
October 6, 2005: Two new Thio-Arsenosugars found in Scallops

Further chapters on techniques and methodology for speciation analysis:

Chapter 1: Tools for elemental speciation
Chapter 2: ICP-MS - A versatile detection system for speciation analysis
Chapter 3: LC-ICP-MS - The most often used hyphenated system for speciation analysis
Chapter 4: GC-ICP-MS- A very sensitive hyphenated system for speciation analysis
Chapter 5: CE-ICP-MS for speciation analysis
Chapter 6: ESI-MS: The tool for the identification of species
Chapter 7: Speciation Analysis - Striving for Quality
Chapter 8: Atomic Fluorescence Spectrometry as a Detection System for Speciation Analysis
Chapter 9: Gas chromatography for the separation of elemental species
Chapter 10: Plasma source detection techniques for gas chromatography
Chapter 11: Fractionation as a first step towards speciation analysis
Chapter 12: Flow-injection inductively coupled plasma mass spectrometry for speciation analysis
Chapter 13: Gel electrophoresis combined with laser ablation inductively coupled plasma mass spectrometry for speciation analysis
Chapter 14: Non-chromatographic separation techniques for speciation analysis

last time modified: January 14, 2024


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