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Hyphenation of packed column supercritical fluid chromatography with mass spectrometry: where are we and what are the remaining challenges?

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Abstract

Over the last decades, packed column supercritical fluid chromatography (pSFC) using carbon dioxide (CO2) as supercritical fluid has gained interest as a complementary separation technique to liquid chromatography (LC). Various commercial solutions for the hyphenation to atmospheric pressure ionization (API) including electrospray (ESI) and atmospheric pressure chemical ionization (APCI) have been described using split-flow or full-flow introduction approaches. This review discusses various aspects of the hyphenation using these two approaches. It also illustrates the difference between LC-MS and SFC-MS. The benefits and challenges of the decoupling of the separation mobile phase from the ionization conditions are also pointed out. The effect of CO2 on ESI performance and the adduct reduction are also discussed. Finally, limitation of current hardware and the limited use of smaller column internal diameters (i.d.) are discussed.

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References

  1. Klesper E, Corwin AH, Turner DA. High pressure gas chromatography above critical temperatures. J Org Chem. 1962;27(2):700–1.

    Article  CAS  Google Scholar 

  2. Lesellier E, West C. The many faces of packed column supercritical fluid chromatography – a critical review. J Chromatogr A. 2015;1382:2–46. https://doi.org/10.1016/j.chroma.2014.12.083.

    Article  CAS  PubMed  Google Scholar 

  3. Fjeldsted JC, Lee ML. Capillary supercritical fluid chromatography. Anal Chem. 1984;56(4):619–28. https://doi.org/10.1021/ac00268a004.

    Article  Google Scholar 

  4. Smith RD, Kalinoski HT, Udseth HR. Fundamentals and practice of supercritical fluid chromatography-mass spectrometry. Mass Spectrom Rev. 1987;6(4):445–96. https://doi.org/10.1002/mas.1280060402.

    Article  CAS  Google Scholar 

  5. Chollet C, Boutet-Mercey S, Laboureur L, Rincon C, Méjean M, Jouhet J, et al. Supercritical fluid chromatography coupled to mass spectrometry for lipidomics. J Mass Spectrom. 2019;54(10):791–801. https://doi.org/10.1002/jms.4445.

    Article  CAS  PubMed  Google Scholar 

  6. Niessen WMA. Chapter 1. Developments in interface technology for combined liquid chromatography, capillary electrophoresis and supercritical fluid chromatography-mass spectrometry. In: Barceló D, editor. J Chromatogr Lib. Elsevier; 1996. p. 3–70.

  7. Huang E, Henion J, Covey TR. Packed-column supercritical fluid chromatography—mass spectrometry and supercritical fluid chromatography—tandem mass spectrometry with ionization at atmospheric pressure. J Chromatogr A. 1990;511:257–70. https://doi.org/10.1016/S0021-9673(01)93289-3.

    Article  Google Scholar 

  8. Tyrefors LN, Moulder RX, Markides KE. Interface for open tubular column supercritical fluid chromatography/atmospheric pressure chemical ionization mass spectrometry. Anal Chem. 1993;65(20):2835–40. https://doi.org/10.1021/ac00068a021.

    Article  CAS  Google Scholar 

  9. Sadoun F, Virelizier H, Arpino PJ. Packed-column supercritical fluid chromatography coupled with electrospray ionization mass spectrometry. J Chromatogr A. 1993;647(2):351–9. https://doi.org/10.1016/0021-9673(93)83415-O.

    Article  CAS  Google Scholar 

  10. Tarafder A. Designs and methods for interfacing SFC with MS. J Chromatogr B. 2018;1091:1–13. https://doi.org/10.1016/j.jchromb.2018.05.003.

    Article  CAS  Google Scholar 

  11. Guillarme D, Desfontaine V, Heinisch S, Veuthey J-L. What are the current solutions for interfacing supercritical fluid chromatography and mass spectrometry? J Chromatogr B. 2018;1083:160–70. https://doi.org/10.1016/j.jchromb.2018.03.010.

    Article  CAS  Google Scholar 

  12. Grand-Guillaume Perrenoud A, Veuthey J-L, Guillarme D. Coupling state-of-the-art supercritical fluid chromatography and mass spectrometry: from hyphenation interface optimization to high-sensitivity analysis of pharmaceutical compounds. J Chromatogr A. 2014;1339:174–84. https://doi.org/10.1016/j.chroma.2014.03.006.

    Article  CAS  PubMed  Google Scholar 

  13. Pinkston JD. Advantages and drawbacks of popular supercritical fluid chromatography/mass interfacing approaches--a user’s perspective. Eur J Mass Spectrom. 2005;11(2):189–97. https://doi.org/10.1255/ejms.731.

    Article  CAS  Google Scholar 

  14. Hoke SH, Tomlinson JA, Bolden RD, Morand KL, Pinkston JD, Wehmeyer KR. Increasing bioanalytical throughput using pcSFC-MS/MS: 10 minutes per 96-well plate. Anal Chem. 2001;73(13):3083–8. https://doi.org/10.1021/ac0014820.

    Article  CAS  PubMed  Google Scholar 

  15. Chester TL, Pinkston JD. Pressure-regulating fluid interface and phase behavior considerations in the coupling of packed-column supercritical fluid chromatography with low-pressure detectors. J Chromatogr A. 1998;807(2):265–73. https://doi.org/10.1016/S0021-9673(98)00082-X.

    Article  CAS  Google Scholar 

  16. Bolaños BJB, Ventura MCM, Greig MJM. Preserving the chromatographic integrity of high-speed supercritical fluid chromatography separations using time-of-flight mass spectrometry. J Comb Chem. 2003;5(4):451–5.

    Article  CAS  PubMed  Google Scholar 

  17. Hopfgartner G, Bean K, Henion J, Henry R. Ion spray mass spectrometric detection for liquid chromatography: a concentration- or a mass-flow-sensitive device? J Chromatogr A. 1993;647(1):51–61. https://doi.org/10.1016/0021-9673(93)83323-k.

    Article  CAS  Google Scholar 

  18. Petruzziello F, Grand-Guillaume Perrenoud A, Thorimbert A, Fogwill M, Rezzi S. Quantitative profiling of endogenous fat-soluble vitamins and carotenoids in human plasma using an improved UHPSFC-ESI-MS interface. Anal Chem. 2017;89(14):7615–22. https://doi.org/10.1021/acs.analchem.7b01476.

    Article  CAS  PubMed  Google Scholar 

  19. Akbal L, Hopfgartner G. Effects of liquid post-column addition in electrospray ionization performance in supercritical fluid chromatography–mass spectrometry. J Chromatogr A. 2017;1517:176–84. https://doi.org/10.1016/j.chroma.2017.08.044.

    Article  CAS  PubMed  Google Scholar 

  20. Nováková L, Rentsch M, Grand-Guillaume Perrenoud A, Nicoli R, Saugy M, Veuthey JL, et al. Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of do** agents. II: analysis of biological samples. Anal Chim Acta. 2015;853:647–59. https://doi.org/10.1016/j.aca.2014.10.007.

    Article  CAS  PubMed  Google Scholar 

  21. Broeckling CD, Ganna A, Layer M, Brown K, Sutton B, Ingelsson E, et al. Enabling efficient and confident annotation of LC-MS metabolomics data through MS1 spectrum and time prediction. Anal Chem. 2016;88(18):9226–34. https://doi.org/10.1021/acs.analchem.6b02479.

    Article  CAS  PubMed  Google Scholar 

  22. Mahieu NG, Patti GJ. Systems-level annotation of a metabolomics data set reduces 25000 features to fewer than 1000 unique metabolites. Anal Chem. 2017;89(19):10397–406. https://doi.org/10.1021/acs.analchem.7b02380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bonner R, Stricker T, Hopfgartner G. Adduct ions in electrospray ionization: what are they and why should we care? Proceedings of the 67th ASMS Conference on Mass Spectrometry and Allied Topics, San Diego, CA.

  24. Desfontaine V, Losacco GL, Gagnebin Y, Pezzatti J, Farrell WP, González-Ruiz V, et al. Applicability of supercritical fluid chromatography – mass spectrometry to metabolomics. I – optimization of separation conditions for the simultaneous analysis of hydrophilic and lipophilic substances. J Chromatogr A. 2018;1562:96–107. https://doi.org/10.1016/j.chroma.2018.05.055.

    Article  CAS  PubMed  Google Scholar 

  25. Matuszewski BK, Constanzer ML, Chavez-Eng CM. Matrix effect in quantitative LC/MS/MS analyses of biological fluids: a method for determination of finasteride in human plasma at picogram per milliliter concentrations. Anal Chem. 1998;70(5):882–9. https://doi.org/10.1021/ac971078+.

    Article  CAS  PubMed  Google Scholar 

  26. Kebarle P, Tang L. From ions in solution to ions in the gas phase - the mechanism of electrospray mass spectrometry. Anal Chem. 1993;65(22):972A–86A. https://doi.org/10.1021/ac00070a001.

    Article  CAS  Google Scholar 

  27. 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. https://doi.org/10.1016/j.aca.2017.05.005.

    Article  CAS  PubMed  Google Scholar 

  28. Haglind A, Hedeland M, Arvidsson T, Pettersson CE. Major signal suppression from metal ion clusters in SFC/ESI-MS - cause and effects. J Chromatogr B. 2018;1084:96–105. https://doi.org/10.1016/j.jchromb.2018.03.024.

    Article  CAS  Google Scholar 

  29. Desfontaine V, Capetti F, Nicoli R, Kuuranne T, Veuthey J-L, Guillarme D. Systematic evaluation of matrix effects in supercritical fluid chromatography versus liquid chromatography coupled to mass spectrometry for biological samples. J Chromatogr B. 2018;1079:51–61. https://doi.org/10.1016/j.jchromb.2018.01.037.

    Article  CAS  Google Scholar 

  30. Riddell N, van Bavel B, Ericson Jogsten I, McCrindle R, McAlees A, Chittim B. Coupling supercritical fluid chromatography to positive ion atmospheric pressure ionization mass spectrometry: ionization optimization of halogenated environmental contaminants. Intl J Mass Spectrom. 2017;421:156–63. https://doi.org/10.1016/j.ijms.2017.07.005.

    Article  CAS  Google Scholar 

  31. West C, Melin J, Ansouri H, Mengue MM. Unravelling the effects of mobile phase additives in supercritical fluid chromatography. Part I: polarity and acidity of the mobile phase. J Chromatogr A. 2017;1492:136–43. https://doi.org/10.1016/j.chroma.2017.02.066.

    Article  CAS  PubMed  Google Scholar 

  32. Desfontaine V, Nováková L, Ponzetto F, Nicoli R, Saugy M, Veuthey J-L, et al. Liquid chromatography and supercritical fluid chromatography as alternative techniques to gas chromatography for the rapid screening of anabolic agents in urine. J Chromatogr A. 2016;1451:145–55. https://doi.org/10.1016/j.chroma.2016.05.004.

    Article  CAS  PubMed  Google Scholar 

  33. Desfontaine V, Tarafder A, Hill J, Fairchild J, Grand-Guillaume Perrenoud A, Veuthey JL, et al. A systematic investigation of sample diluents in modern supercritical fluid chromatography. J Chromatogr A. 2017;1511:122–31. https://doi.org/10.1016/j.chroma.2017.06.075.

    Article  CAS  PubMed  Google Scholar 

  34. Glenne E, Samuelsson J, Leek H, Forssen P, Klarqvist M, Fornstedt T. Systematic investigations of peak distortions due to additives in supercritical fluid chromatography. J Chromatogr A. 2020;461048. https://doi.org/10.1016/j.chroma.2020.461048.

  35. Fujito Y, Hayakawa Y, Izumi Y, Bamba T. Importance of optimizing chromatographic conditions and mass spectrometric parameters for supercritical fluid chromatography/mass spectrometry. J Chromatogr A. 2017;1508:138–47. https://doi.org/10.1016/j.chroma.2017.05.071.

    Article  CAS  PubMed  Google Scholar 

  36. Svan A, Hedeland M, Arvidsson T, Pettersson CE. The differences in matrix effect between supercritical fluid chromatography and reversed phase liquid chromatography coupled to ESI/MS. Anal Chim Acta. 2018;1000:163–71. https://doi.org/10.1016/j.aca.2017.10.014.

    Article  CAS  PubMed  Google Scholar 

  37. Laboureur L, Bonneau N, Champy P, Brunelle A, Touboul D. Structural characterisation of acetogenins from Annona muricata by supercritical fluid chromatography coupled to high-resolution tandem mass spectrometry. Phytochem Anal. 2017;28(6):512–20. https://doi.org/10.1002/pca.2700.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Gérard Hopfgartner.

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Akbal, L., Hopfgartner, G. Hyphenation of packed column supercritical fluid chromatography with mass spectrometry: where are we and what are the remaining challenges?. Anal Bioanal Chem 412, 6667–6677 (2020). https://doi.org/10.1007/s00216-020-02715-4

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