Advertisement

Analytical and Bioanalytical Chemistry

, Volume 411, Issue 16, pp 3533–3542 | Cite as

ESI outcompetes other ion sources in LC/MS trace analysis

  • Asko LaanisteEmail author
  • Ivo Leito
  • Anneli Kruve
Research Paper

Abstract

Choosing an appropriate ion source is a crucial step in liquid chromatography mass spectrometry (LC/MS) method development. In this paper, we compare four ion sources for LC/MS analysis of 40 pesticides in tomato and garlic matrices. We compare electrospray ionisation (ESI) source, thermally focused/heated electrospray (HESI), atmospheric pressure photoionisation (APPI) source with and without dopant, and multimode source in ESI mode, atmospheric pressure chemical ionisation (APCI) mode, and combined mode using both ESI and APCI, i.e. altogether seven different ionisation modes. The lowest limits of detection (LoDs) were obtained by ESI and HESI. Widest linear ranges were observed with the conventional ESI source without heated nebuliser gas. In comparison to HESI, ESI source was significantly less affected by matrix effect. APPI ranked second (after ESI) by not being influenced by matrix effect; therefore, it would be a good alternative to ESI if low LoDs are not required.

Graphical abstract

Keywords

Ion source Pesticide Heated electrospray APPI Multimode 

Abbreviations

APPI

Atmospheric pressure photoionisation

DA-APPI

Dopant-assisted APPI

HESI

Thermally focused/heated electrospray

MMI

Multimode ionisation

Notes

Funding information

This work was supported by Personal Research Funding Project 34 and the institutional research funding IUT20-14 (TLOKT14014I) from the Estonian Research Council.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1832_MOESM1_ESM.pdf (1.2 mb)
ESM 1 (PDF 1275 kb)

References

  1. 1.
    Dole M. Molecular beams of macroions. J Chem Phys. 1968;49:2240–9.CrossRefGoogle Scholar
  2. 2.
    Whitehouse CM, Dreyer RN, Yamashita M, Fenn JB. Electrospray interface for liquid chromatographs and mass spectrometers. Anal Chem. 1985;57:675–9.CrossRefGoogle Scholar
  3. 3.
    Gross JH. Mass spectrometry. 2nd ed. Heidelberg: Springer; 2011.CrossRefGoogle Scholar
  4. 4.
    Covey TR, Thomson BA, Schneider BB. Atmospheric pressure ion sources. Mass Spectrom Rev. 2009;28:870–97.CrossRefGoogle Scholar
  5. 5.
    Robb DB, Covey TR, Bruins AP. Atmospheric pressure photoionization: an ionization method for liquid chromatography−mass spectrometry. Anal Chem. 2000;72:3653–9.CrossRefGoogle Scholar
  6. 6.
    Stahnke H, Kittlaus S, Kempe G, Hemmerling C, Alder L. The influence of electrospray ion source design on matrix effects: influence of ESI source design on matrix effects. J Mass Spectrom. 2012;47:875–84.CrossRefGoogle Scholar
  7. 7.
    Mordehai A, Fjeldsted J. Agilent Jet Stream Thermal Gradient Focusing Technology. Agilent Technologies. 2009. https://www.agilent.com/cs/library/technicaloverviews/Public/5990-3494en_lo CMS.pdf. Accessed 06 Feb 2019.
  8. 8.
    HESI-II Probe User Guide. Thermo fisher scientific. 2009. http://tools.thermofisher.com/content/sfs/manuals/hesi_ii_probe_user.pdf. Accessed 06 Feb 2019.
  9. 9.
    API 4000™ LC/MS/MS System. AB Sciex. 2010. https://sciex.com/documents/downloads/literature/4000-api-hardware-guide.pdf. Accessed 06 Feb 2019.
  10. 10.
    Wolrab D, Frühauf P, Gerner C. Direct coupling of supercritical fluid chromatography with tandem mass spectrometry for the analysis of amino acids and related compounds: comparing electrospray ionization and atmospheric pressure chemical ionization. Anal Chim Acta. 2017;981:106–15.CrossRefGoogle Scholar
  11. 11.
    Asperger A, Efer J, Koal T, Engewald W. On the signal response of various pesticides in electrospray and atmospheric pressure chemical ionization depending on the flow-rate of eluent applied in liquid chromatography–tandem mass spectrometry. J Chromatogr A. 2001;937:65–72.CrossRefGoogle Scholar
  12. 12.
    Schiewek R, Lorenz M, Giese R, Brockmann K, Benter T, Gäb S, et al. Development of a multipurpose ion source for LC-MS and GC-API MS. Anal Bioanal Chem. 2008;392:87–96.CrossRefGoogle Scholar
  13. 13.
    Galaon T, Vacaresteanu C, Anghel D-F, David V. Simultaneous ESI-APCI(+) ionization and fragmentation pathways for nine benzodiazepines and zolpidem using single quadrupole LC-MS: simultaneous ESI-APCI(+) ionization and fragmentation pathways. Drug Test Anal. 2013;6:439–50.Google Scholar
  14. 14.
    Tölgyesi Á, Kunsági Z. Quantification of T-2 and HT-2 mycotoxins in cereals by liquid chromatography-multimode ionization-tandem mass spectrometry. Microchem J. 2013;106:300–6.CrossRefGoogle Scholar
  15. 15.
    Short LC, Hanold KA, Cai S-S, Syage JA. Electrospray ionization/atmospheric pressure photoionization multimode source for low-flow liquid chromatography/mass spectrometric analysis. Rapid Commun Mass Spectrom. 2007;21:1561–6.CrossRefGoogle Scholar
  16. 16.
    Lien G-W, Chen C-Y, Wang G-S. Comparison of electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization for determining estrogenic chemicals in water by liquid chromatography tandem mass spectrometry with chemical derivatizations. J Chromatogr A. 2009;1216:956–66.CrossRefGoogle Scholar
  17. 17.
    Rauha J-P, Vuorela H, Kostiainen R. Effect of eluent on the ionization efficiency of flavonoids by ion spray, atmospheric pressure chemical ionization, and atmospheric pressure photoionization mass spectrometry. J Mass Spectrom. 2001;36:1269–80.CrossRefGoogle Scholar
  18. 18.
    Thurman EM, Ferrer I, Barceló D. Choosing between atmospheric pressure chemical ionization and electrospray ionization interfaces for the HPLC/MS analysis of pesticides. Anal Chem. 2001;73:5441–9.CrossRefGoogle Scholar
  19. 19.
    Leinonen A, Kuuranne T, Kostiainen R. Liquid chromatography/mass spectrometry in anabolic steroid analysis? Optimization and comparison of three ionization techniques: electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization. J Mass Spectrom. 2002;37:693–8.CrossRefGoogle Scholar
  20. 20.
    Maragou NC, Thomaidis NS, Koupparis MA. Optimization and comparison of ESI and APCI LC-MS/MS methods: a case study of Irgarol 1051, Diuron, and their degradation products in environmental samples. J Am Soc Mass Spectrom. 2011;22:1826–38.CrossRefGoogle Scholar
  21. 21.
    Gilbert-López B, Geltenpoth H, Meyer C, Michels A, Hayen H, Molina-Díaz A, et al. Performance of dielectric barrier discharge ionization mass spectrometry for pesticide testing: a comparison with atmospheric pressure chemical ionization and electrospray ionization: performance of DBDI-MS for pesticide testing. Rapid Commun Mass Spectrom. 2013;27:419–29.CrossRefGoogle Scholar
  22. 22.
    Keski-Rahkonen P, Huhtinen K, Desai R, Tim Harwood D, Handelsman DJ, Poutanen M, et al. LC-MS analysis of estradiol in human serum and endometrial tissue: comparison of electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization: comparison of ESI, APCI and APPI for E2 analysis. J Mass Spectrom. 2013;48:1050–8.CrossRefGoogle Scholar
  23. 23.
    Guo T, Shi Y, Zheng L, Feng F, Zheng F, Liu W. Rapid and simultaneous determination of sulfonate ester genotoxic impurities in drug substance by liquid chromatography coupled to tandem mass spectrometry: comparison of different ionization modes. J Chromatogr A. 2014;1355:73–9.CrossRefGoogle Scholar
  24. 24.
    Garcia-Ac A, Segura PA, Viglino L, Gagnon C, Sauvé S. Comparison of APPI, APCI and ESI for the LC-MS/MS analysis of bezafibrate, cyclophosphamide, enalapril, methotrexate and orlistat in municipal wastewater. J Mass Spectrom. 2011;46:383–90.CrossRefGoogle Scholar
  25. 25.
    Rybak ME, Parker DL, Pfeiffer CM. Determination of urinary phytoestrogens by HPLC–MS/MS: a comparison of atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). J Chromatogr B. 2008;861:145–50.CrossRefGoogle Scholar
  26. 26.
    Straube EA, Dekant W, Völkel W. Comparison of electrospray ionization, atmospheric pressure chemical ionization, and atmospheric pressure photoionization for the analysis of dinitropyrene and aminonitropyrene LC-MS/MS. J Am Soc Mass Spectrom. 2004;15:1853–62.CrossRefGoogle Scholar
  27. 27.
    Cai S-S, Syage JA. Comparison of atmospheric pressure photoionization, atmospheric pressure chemical ionization, and electrospray ionization mass spectrometry for analysis of lipids. Anal Chem. 2006;78:1191–9.CrossRefGoogle Scholar
  28. 28.
    Cai S-S, Hanold KA, Syage JA. Comparison of atmospheric pressure photoionization and atmospheric pressure chemical ionization for normal-phase LC/MS chiral analysis of pharmaceuticals. Anal Chem. 2007;79:2491–8.CrossRefGoogle Scholar
  29. 29.
    Himmelsbach M, Buchberger W, Reingruber E. Determination of polymer additives by liquid chromatography coupled with mass spectrometry. A comparison of atmospheric pressure photoionization (APPI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI). Polym Degrad Stab. 2009;94:1213–9.CrossRefGoogle Scholar
  30. 30.
    Kauppila TJ, Nikkola T, Ketola RA, Kostiainen R. Atmospheric pressure photoionization-mass spectrometry and atmospheric pressure chemical ionization-mass spectrometry of neurotransmitters. J Mass Spectrom. 2006;41:781–9.CrossRefGoogle Scholar
  31. 31.
    Wang I-T, Feng Y-T, Chen C-Y. Determination of 17 illicit drugs in oral fluid using isotope dilution ultra-high performance liquid chromatography/tandem mass spectrometry with three atmospheric pressure ionizations. J Chromatogr B. 2010;878:3095–105.CrossRefGoogle Scholar
  32. 32.
    Cavaliere C, Foglia P, Pastorini E, Samperi R, Laganà A. Liquid chromatography/tandem mass spectrometric confirmatory method for determining aflatoxin M1 in cow milk. J Chromatogr A. 2006;1101:69–78.CrossRefGoogle Scholar
  33. 33.
    Titato GM, Bicudo RC, Lanças FM. Optimization of the ESI and APCI experimental variables for the LC/MS determination of s-triazines, methylcarbamates, organophosphorous, benzimidazoles, carboxamide and phenylurea compounds in orange samples. J Mass Spectrom. 2007;42:1348–57.CrossRefGoogle Scholar
  34. 34.
    Commisso M, Anesi A, Dal Santo S, Guzzo F. Performance comparison of electrospray ionization and atmospheric pressure chemical ionization in untargeted and targeted liquid chromatography/mass spectrometry based metabolomics analysis of grapeberry metabolites: APCI well ionizes strongly polar metabolites. Rapid Commun Mass Spectrom. 2017;31:292–300.CrossRefGoogle Scholar
  35. 35.
    Hagenhoff S, Hayen H. LC/MS analysis of vitamin D metabolites by dielectric barrier discharge ionization and a comparison with electrospray ionization and atmospheric pressure chemical ionization. Anal Bioanal Chem. 2018;410:4905–11.CrossRefGoogle Scholar
  36. 36.
    Wang R, Zhang L, Zhang Z, Tian Y. Comparison of ESI– and APCI–LC–MS/MS methods: a case study of levonorgestrel in human plasma. J Pharm Anal. 2016;6:356–62.CrossRefGoogle Scholar
  37. 37.
    Fredenhagen A, Kühnöl J. Evaluation of the optimization space for atmospheric pressure photoionization (APPI) in comparison with APCI: evaluation of the optimization space for APPI. J Mass Spectrom. 2014;49:727–36.CrossRefGoogle Scholar
  38. 38.
    Xu X, Mei H, Wang S, Zhou Q, Wang G, Broske L, et al. A study of common discovery dosing formulation components and their potential for causing time-dependent matrix effects in high-performance liquid chromatography tandem mass spectrometry assays. Rapid Commun Mass Spectrom. 2005;19:2643–50.CrossRefGoogle Scholar
  39. 39.
    Ross MS, Wong CS. Comparison of electrospray ionization, atmospheric pressure photoionization, and anion attachment atmospheric pressure photoionization for the analysis of hexabromocyclododecane enantiomers in environmental samples. J Chromatogr A. 2010;1217:7855–63.CrossRefGoogle Scholar
  40. 40.
    Souverain S, Rudaz S, Veuthey J-L. Matrix effect in LC-ESI-MS and LC-APCI-MS with off-line and on-line extraction procedures. J Chromatogr A. 2004;1058:61–6.CrossRefGoogle Scholar
  41. 41.
    Hakala KS, Laitinen L, Kaukonen AM, Hirvonen J, Kostiainen R, Kotiaho T. Development of LC/MS/MS methods for cocktail dosed Caco-2 samples using atmospheric pressure photoionization and electrospray ionization. Anal Chem. 2003;75:5969–77.CrossRefGoogle Scholar
  42. 42.
    Gosetti F, Mazzucco E, Zampieri D, Gennaro MC. Signal suppression/enhancement in high-performance liquid chromatography tandem mass spectrometry. J Chromatogr A. 2010;1217:3929–37.CrossRefGoogle Scholar
  43. 43.
    Kruve A, Leito I. Comparison of different methods aiming to account for/overcome matrix effects in LC/ESI/MS on the example of pesticide analyses. Anal Methods. 2013;5:3035.CrossRefGoogle Scholar
  44. 44.
    Sandra K, dos Pereira AS, Vanhoenacker G, David F, Sandra P. Comprehensive blood plasma lipidomics by liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr A. 2010;1217:4087–99.CrossRefGoogle Scholar
  45. 45.
    Jarmusch AK, Musso AM, Shymanovich T, Jarmusch SA, Weavil MJ, Lovin ME, et al. Comparison of electrospray ionization and atmospheric pressure photoionization liquid chromatography mass spectrometry methods for analysis of ergot alkaloids from endophyte-infected sleepygrass (Achnatherum robustum). J Pharm Biomed Anal. 2016;117:11–7.CrossRefGoogle Scholar
  46. 46.
    Parr MK, Wüst B, Teubel J, Joseph JF. Splitless hyphenation of SFC with MS by APCI, APPI, and ESI exemplified by steroids as model compounds. J Chromatogr B. 2018;1091:67–78.CrossRefGoogle Scholar
  47. 47.
    Lehotay SJ, Maštovská K, Lightfield AR. Use of buffering and other means to improve results of problematic pesticides in a fast and easy method for residue analysis of fruits and vegetables. J AOAC Int. 2005;88:615–29.Google Scholar
  48. 48.
    SANTE/11813/2017: Guidance document on analytical quality control and method validation procedures for pesticide residues and analysis in food and feed. European Commission. 2017. https://ec.europa.eu/food/sites/food/files/plant/docs/pesticides_mrl_guidelines_wrkdoc_2017-11813.pdf. Accessed 06 Feb 2019.
  49. 49.
    International Conference of harmonization of technical requirements for registration of pharmaceuticals for human use. Validation of analytical procedures: text and methodology Q2(R1). 2005. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf. Accessed 06 Feb 2019.
  50. 50.
    Kruve A, Rebane R, Kipper K, Oldekop M-L, Evard H, Herodes K, et al. Tutorial review on validation of liquid chromatography–mass spectrometry methods: part I. Anal Chim Acta. 2015;870:29–44.CrossRefGoogle Scholar
  51. 51.
    Evard H, Kruve A, Leito I. Tutorial on estimating the limit of detection using LC-MS analysis, part I: theoretical review. Anal Chim Acta. 2016;942:23–39.CrossRefGoogle Scholar
  52. 52.
    Evard H, Kruve A, Leito I. Tutorial on estimating the limit of detection using LC-MS analysis, part II: practical aspects. Anal Chim Acta. 2016;942:40–9.CrossRefGoogle Scholar
  53. 53.
    International vocabulary of metrology – basic and general concepts and associated terms (VIM). 3rd edition. Joint Committee for Guides in Metrology. 2012. https://www.bipm.org/utils/common/documents/jcgm/JCGM_200_2012.pdf. Accessed 06 Feb 2019.
  54. 54.
    Kruve A, Rebane R, Kipper K, Oldekop M-L, Evard H, Herodes K, et al. Tutorial review on validation of liquid chromatography–mass spectrometry methods: part II. Anal Chim Acta. 2015;870:8–28.CrossRefGoogle Scholar
  55. 55.
    Kruve A, Herodes K, Leito I. Optimization of electrospray interface and quadrupole ion trap mass spectrometer parameters in pesticide liquid chromatography/electrospray ionization mass spectrometry analysis. Rapid Commun Mass Spectrom. 2010;24:919–26.CrossRefGoogle Scholar
  56. 56.
    Lorenz M, Schiewek R, Brockmann KJ, Schmitz OJ, Gäb S, Benter T. The distribution of ion acceptance in atmospheric pressure ion sources: spatially resolved APLI measurements. J Am Soc Mass Spectrom. 2008;19:400–10.CrossRefGoogle Scholar
  57. 57.
    Awad H, Khamis MM, El-Aneed A. Mass spectrometry, review of the basics: ionization. Appl Spectrosc Rev. 2015;50:158–75.CrossRefGoogle Scholar
  58. 58.
    Kauppila TJ, Kersten H, Benter T. The ionization mechanisms in direct and dopant-assisted atmospheric pressure photoionization and atmospheric pressure laser ionization. J Am Soc Mass Spectrom. 2014;25:1870–81.CrossRefGoogle Scholar
  59. 59.
    Ghosh C, Shinde CP, Chakraborty BS. Influence of ionization source design on matrix effects during LC–ESI-MS/MS analysis. J Chromatogr B. 2012;893–894:193–200.CrossRefGoogle Scholar
  60. 60.
    Kebarle P, Verkerk UH. Electrospray: from ions in solution to ions in the gas phase, what we know now. Mass Spectrom Rev. 2009;28:898–917.CrossRefGoogle Scholar
  61. 61.
    Kruve A. Influence of mobile phase, source parameters and source type on electrospray ionization efficiency in negative ion mode: influence of mobile phase in ESI/MS. J Mass Spectrom. 2016;51:596–601.CrossRefGoogle Scholar
  62. 62.
    Enke CG. A predictive model for matrix and analyte effects in electrospray ionization of singly-charged ionic analytes. Anal Chem. 1997;69:4885–93.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of ChemistryUniversity of TartuTartuEstonia

Personalised recommendations