A New Matrix Assisted Ionization Method for the Analysis of Volatile and Nonvolatile Compounds by Atmospheric Probe Mass Spectrometry

  • Shubhashis Chakrabarty
  • Vincent S. Pagnotti
  • Ellen D. Inutan
  • Sarah Trimpin
  • Charles N. McEwen
Research Article

Abstract

Matrix assisted ionization of nonvolatile compounds is shown not to be limited to vacuum conditions and does not require a laser. Simply placing a solution of analyte dissolved with a suitable matrix such as 3-nitrobenzonitrile (3-NBN) or 2,5-dihydroxyacetophenone on a melting point tube and gently heating the dried sample near the ion entrance aperture of a mass spectrometer using a flow of gas produces abundant ions of peptides, small proteins, drugs, and polar lipids. Fundamental studies point to matrix-mediated ionization occurring prior to the entrance aperture of the mass spectrometer. The method is analytically useful, producing peptide mass fingerprints of bovine serum albumin tryptic digest consuming sub-picomoles of sample. Application of 100 fmol of angiotensin I in 3-NBN matrix produces the doubly and triply protonated molecular ions as the most abundant peaks in the mass spectrum. No carryover is observed for samples containing up to 100 pmol of this peptide. A commercial atmospheric samples analysis probe provides a simple method for sample introduction to an atmospheric pressure ion source for analysis of volatile and nonvolatile compounds without using the corona discharge but using sample preparation similar to matrix-assisted laser desorption/ionization.

Key words

Nonvolatile compounds Peptides Drugs Lipids Mass spectrometry Matrix assisted Probe introduction 

Supplementary material

13361_2013_634_MOESM1_ESM.doc (1.5 mb)
Supporting InformationFigures showing mass spectra of bradykinin using 3-NBN, 2,5-DHAP, and 2,5-DHB, and angiotensin I, insulin, sphingomyelin, verapamil, hydroxycortisone, and hydroxychloroquine using 3-NBN with ASAP probe introduction are presented along with mass spectra of levofloxacin, ubiquitin, myoglobin, and saliva using 3-NBN and a voltage applied to the HESI probe. The mass spectrum of bradykinin using a Waters Xevo TQ-S mass spectrometer without an ASAP probe is also provided. (DOC 1513 kb)

References

  1. 1.
    Watson, J.T., Sparkman, O.D.: Introduction to Mass Spectrometry: Instrumentation; Applications and Strategies for Data Interpretation, 4th edn. Wiley, New York (2007)CrossRefGoogle Scholar
  2. 2.
    Cody, R.B., Laramée, J.A., Durst, H.D.: Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal. Chem. 77, 2297–2302 (2005)Google Scholar
  3. 3.
    McEwen, C.N., McKay, R.G., Larsen, B.S.: Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments. Anal. Chem. 77, 7826–7831 (2005)Google Scholar
  4. 4.
    Saha, S., Chen, L.C., Mandal, M.K., Hiraoka, K.: Leidenfrost phenomenon-assisted thermal desorption (LPTD) and its application to open ion sources at atmospheric pressure mass spectrometry. J. Am. Soc. Mass Spectrom. 24, 341–347 (2013)CrossRefGoogle Scholar
  5. 5.
    Karas, M., Bachman, D., Bahr, U., Hillenkamp, F.: Matrix-assisted ultraviolet laser desorption of non-volatile compounds. Int. J. Mass Spectrom. Ion Processes. 78, 53–68 (1987)CrossRefGoogle Scholar
  6. 6.
    Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F., Whitehouse, C.M.: Electrospray ionization for analysis of large molecules. Science 246, 64–67 (1989)CrossRefGoogle Scholar
  7. 7.
    Venter, A., Nefliu, M., Cooks, R.G.: Ambient desorption ionization mass spectrometry. Trends Anal. Chem. 27, 284–290 (2008)CrossRefGoogle Scholar
  8. 8.
    Takats, Z., Wiseman, J.M., Gologan, B., Cooks, R.G.: Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306, 471–473 (2004)CrossRefGoogle Scholar
  9. 9.
    Shiea, J., Huang, M.-Z., Hsu, C.-Y., Lee, C.-H., Yuan, I., Beech, J.: Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids. Rapid Commun. Mass Spectrom. 19, 3701–3704 (2005)CrossRefGoogle Scholar
  10. 10.
    Chen, H., Venter, A., Cooks, R.G.: Extractive electrospray ionization for direct analysis of undiluted urine, milk, and other complex mixtures without sample preparation. Chem.Commun. 2042–2044 (2006)Google Scholar
  11. 11.
    Hiraoka, K., Nishidate, K., Mori, K., Asakawa, D., Suzuki, S.: Development of probe electrospray using a solid needle. Rapid Commun. Mass Spectrom. 21, 3139–3144 (2007)CrossRefGoogle Scholar
  12. 12.
    Mandal, M.K., Chen, L.C., Yu, Z., Nonami, H., Erra-Balsells, R., Hiraoka, K.: Detection of protein from detergent solutions by probe electrospray ionization mass spectrometry (PESI-MS). J. Mass Spectrom. 46, 967–975 (2011)CrossRefGoogle Scholar
  13. 13.
    Wang, H., Liu, J., Cooks, R.G., Ouyang, Z.: Paper spray for direct analysis of complex mixtures using mass spectrometry. Angew Chem 122, 889–892 (2010)CrossRefGoogle Scholar
  14. 14.
    Hu, B., So, P.K., Chen, H., Yao, Z.P.: Electrospray ionization using wooden tips. Anal Chem 83, 8201–8207 (2011)CrossRefGoogle Scholar
  15. 15.
    Liu, J., Wang, H., Cooks, R.G., Ouyang, Z.: Leaf spray: Direct chemical analysis of plant material and living plants by mass spectrometry. Anal. Chem. 83, 7608–7613 (2011)Google Scholar
  16. 16.
    Trimpin, S., Inutan, E.D., Herath, T.N., McEwen, C.N.: Laserspray ionization—a new AP-MALDI method for producing highly charged gas-phase ions of peptides and proteins directly from solid solutions. Mol. Cell. Proteomics 9, 362–367 (2010)Google Scholar
  17. 17.
    Trimpin, S., Inutan, E.D., Herath, T.N., McEwen, C.N.: Matrix-assisted laser desorption/ionization mass spectrometry method for selectively producing either singly or multiply charged molecular ions. Anal Chem 82, 11–15 (2010)CrossRefGoogle Scholar
  18. 18.
    McEwen, C.N., Pagnotti, V.S., Inutan, E.D., Trimpin, S.: New paradigm in ionization: Multiply charged ion formation from a solid matrix without a laser or voltage. Anal Chem 82, 9164–9168 (2010)CrossRefGoogle Scholar
  19. 19.
    Inutan, E.D., Wang, B., Trimpin, S.: Commercial intermediate pressure MALDI ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions. Anal Chem 83, 678–684 (2011)CrossRefGoogle Scholar
  20. 20.
    Trimpin, S., Ren, Y., Wang, B., Lietz, C.B., Richards, A.L., Marshall, A.G., Inutan, E.D.: Extending the laserspray ionization concept to produce highly charged ions at high vacuum on a time-of-flight mass analyzer. Anal Chem 83, 5469–5475 (2011)CrossRefGoogle Scholar
  21. 21.
    Inutan, E.D., Trimpin, S.: Matrix assisted ionization vacuum, a new ionization method for biological materials analysis using mass spectrometry. Mol. Cell. Proteomics 12(3), 792–796 (2013)Google Scholar
  22. 22.
    Trimpin, S., Inutan, E.D.: Matrix assisted ionization in vacuum, a widely applicable ionization method for mass spectrometry. J. Am. Soc. Mass Spectrom. doi:10.1007/s13361-012-0571-z (2013)Google Scholar
  23. 23.
    Trimpin, S., Inutan, E.D.: New ionization method for analysis on atmospheric pressure ionization mass spectrometers requiring only vacuum and matrix assistance. Anal. Chem. 85(4), 2005–2009 (2013)Google Scholar
  24. 24.
    Barrere, C., Maire, F., Afonso, C., Giusti, P.: Atmospheric solid analysis probe-ion mobility mass spectrometry of polypropylene. Anal. Chem. 84, 9349–9354 (2012)Google Scholar
  25. 25.
    Lindberg, J., DerMarderosian, A.: A rapid qualitative analysis of natural products by atmospheric solids analysis probe mass spectrometry (ASAP-MS). Planta Medica 78, 1262–1264 (2012)Google Scholar
  26. 26.
    Bruns, E.A., Greaves, J., Finlayson-Pitts, B.J.: Measurement of vapor pressures and heats of sublimation of dicarboxylic acids using atmospheric solids analysis probe mass ppectrometry. J Phys Chem A 116, 5900–5909 (2012)CrossRefGoogle Scholar
  27. 27.
    Rivera, S.M., Canela-Garayoa, R.: Analytical tools for the analysis of carotenoids in diverse materials. J. Chromatogr. A 1224, 1–10 (2012)CrossRefGoogle Scholar
  28. 28.
    Rozenski, J.: Analysis of nucleosides using the atmospheric-pressure solids analysis probe for ionization. Int. J. Mass Spectrom. 304, 204–208 (2011)CrossRefGoogle Scholar
  29. 29.
    Ahmed, A., Cho, Y.J., No, M.H., Koh, J., Tomczyk, N., Giles, K., Yoo, J.S., Kim, S.: Application of the mason-schamp equation and ion mobility mass spectrometry to identify structurally related compounds in crude oil. Anal. Chem. 83, 77–83 (2011)Google Scholar
  30. 30.
    Fussell, R.J., Chan, D., Sharman, M.: An assessment of atmospheric-pressure solids-analysis probes for the detection of chemicals in food. Trends Anal. Chem. 29, 1326–1335 (2010)CrossRefGoogle Scholar
  31. 31.
    Twohig, M., Shockcor, J.P., Wilson, I.D., Nicholson, J.K., Plumb, R.S.: Use of an atmospheric solids analysis probe (ASAP) for high throughput screening of biological fluids: Preliminary applications on urine and bile. J. Proteome Res. 9, 3590–3597 (2010)CrossRefGoogle Scholar
  32. 32.
    Lloyd, J.A., Harron, A.F., McEwen, C.: Combination atmospheric pressure solids analysis probe and desorption electrospray ionization mass spectrometry ion source. Anal. Chem. 81, 9158–9162 (2009)Google Scholar
  33. 33.
    Zydel, F., Trimpin, S., McEwen, C.N.: Laserspray ionization using an atmospheric solids analysis probe for sample introduction. J. Am. Soc. Mass Spectrom. 21, 1889–1892 (2010)Google Scholar
  34. 34.
    Trimpin, S., Wang, B., Inutan, E.D., Li, J., Lietz, C.B., Harron, A.F., Pagnotti, V.S., Sardelis, D., McEwen, C.N.: A mechanism for ionization of nonvolatile compounds in mass spectrometry: Considerations from MALDI and inlet ionization. J. Am. Soc. Mass Spectrom. 23, 1644–1660 (2012)CrossRefGoogle Scholar
  35. 35.
    Gobom, J., Nordhoff, E., Mirgorodskaya, E., Ekman, R., Roepstorff, P.: Sample purification and preparation technique based on nano-scale reversed-phase columns for the sensitive analysis of complex peptide mixtures by matrix-assisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 34, 105–116 (1999)CrossRefGoogle Scholar
  36. 36.
    Krause, J., Stoeckli, M., Schlunegger, U.P.: Studies on the selection of new matrices for ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 10, 1927–1933 (1996)CrossRefGoogle Scholar
  37. 37.
    Halgand, F., Zabrouskov, V., Bassilian, S., Souda, P., Wong, D.T., Loo, J.A., Faull, K.F., Whitelegge, J.P.: Micro-heterogeneity of human saliva peptide P-C characterized by high-resolution top-down Fourier-transform mass spectrometry. J. Am. Soc. Mass Spectrom. 21, 868–877 (2010)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2013

Authors and Affiliations

  • Shubhashis Chakrabarty
    • 1
  • Vincent S. Pagnotti
    • 1
  • Ellen D. Inutan
    • 2
  • Sarah Trimpin
    • 2
  • Charles N. McEwen
    • 1
  1. 1.University of the SciencesPhiladelphiaUSA
  2. 2.Wayne State UniversityDetroitUSA

Personalised recommendations