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Application of Group I Metal Adduction to the Separation of Steroids by Traveling Wave Ion Mobility Spectrometry

  • Alana L. Rister
  • Tiana L. Martin
  • Eric D. DoddsEmail author
Research Article

Abstract

Steroids represent an interesting class of small biomolecules due to their use as biomarkers and their status as scheduled drugs. Although the analysis of steroids is complicated by the potential for many isomers, ion mobility spectrometry (IMS) has previously shown promise for the rapid separation of steroid isomers. This work is aimed at the further development of IMS separation for the analysis of steroids. Here, traveling wave ion mobility spectrometry (TWIMS) was applied to the study of group I metal adducted steroids and their corresponding multimers for five sets of isomers. Each set of isomers had a minimum of one dimeric metal ion adduct that exhibited a resolution greater than one (i.e., approaching baseline resolution). Additionally, ion-neutral collision cross sections (CCSs) were measured using polyalanine as a calibrant, which may provide an additional metric contributing to analyte identification. Where possible, measured CCSs were compared to previously reported values. When measuring CCSs of steroid isomers using polyalanine as the calibrant, nitrogen CCS values were within 1.0% error for monomeric sodiated adducts and slightly higher for the dimeric sodiated adducts. Overall, TWIMS was found to successfully separate steroids as dimeric adducts of group I metals.

Graphical Abstract

Keywords

Steroids Metal ion adduction Isomer discrimination Ion mobility spectrometry Collision cross section 

Notes

Acknowledgements

This work was supported in part by funding from the National Science Foundation, Division of Chemistry, through the Chemical Measurement and Imaging Program (Award Number 1507989) and through the Research Experiences for Undergraduates Program (Award Number 1460829). Funding from the National Institutes of Health, National Institute of General Medical Sciences, was received through a fellowship to A.L.R. from the Molecular Mechanisms of Disease Predoctoral Training Program (Award Number T32GM107001). Finally, the authors thank Jessica L. Minnick and Katherine N. Schumacher for constructive comments on a draft of the manuscript.

Supplementary material

13361_2018_2085_MOESM1_ESM.pdf (358 kb)
ESM 1 (PDF 358 kb)

References

  1. 1.
    Severi, G., Morris, H.A., MacInnis, R.J., English, D.R., Tilley, W., Hopper, J.L., Boyle, P., Giles, G.G.: Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiol. Biomark. Prev. 15, 86–91 (2006)CrossRefGoogle Scholar
  2. 2.
    Morrow, L., Porcu, P.: Neuroactive steroid biomarkers of alcohol sensitivity and alcoholism risk. In: Ritsner, M.S. (ed.) The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes, pp. 47–58. Springer Science+Business Media, Heidelberg (2009)CrossRefGoogle Scholar
  3. 3.
    Hu, J., Zhang, Z., Shen, W.J., Azhar, S.: Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones. Nutr. Metab. 7, 47 (2010)CrossRefGoogle Scholar
  4. 4.
    Haupt, H.A., Rovere, G.D.: Anabolic steroids: a review of the literature. Am. J. Sports Med. 12, 469–484 (1984)CrossRefGoogle Scholar
  5. 5.
    Guddat, S., Thevis, M., Kapron, J., Thomas, A., Schanzer, W.: Application of FAIMS to anabolic androgenic steroids in sport drug testing. Drug Test Anal. 1, 545–553 (2009)CrossRefGoogle Scholar
  6. 6.
    Arlt, W., Biehl, M., Taylor, A.E., Hahner, S., Libe, R., Hughes, B.A., Schneider, P., Smith, D.J., Stiekema, H., Krone, N., Porfiri, E., Opocher, G., Bertherat, J., Mantero, F., Allolio, B., Terzolo, M., Nightingale, P., Shackleton, C.H., Bertagna, X., Fassnacht, M., Stewart, P.M.: Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J. Clin. Endocrinol. Metab. 96, 3775–3784 (2011)CrossRefGoogle Scholar
  7. 7.
    Gouveia, M.J., Brindley, P.J., Santos, L.L., Correia da Costa, J.M., Gomes, P., Vale, N.: Mass spectrometry techniques in the survey of steroid metabolites as potential disease biomarkers: a review. Metabolism. 62, 1206–1217 (2013)CrossRefGoogle Scholar
  8. 8.
    Ray, J.A., Kushnir, M.M., Yost, R.A., Rockwood, A.L., Wayne Meikle, A.: Performance enhancement in the measurement of 5 endogenous steroids by LC-MS/MS combined with differential ion mobility spectrometry. Clin. Chim. Acta. 438, 330–336 (2015)CrossRefGoogle Scholar
  9. 9.
    Alda, M.J., Barceló, D.: Review of analytical methods for the determination of estrogens and progestogens in waste waters. Anal. Chem. 371, 437–447 (2001)CrossRefGoogle Scholar
  10. 10.
    Giese, R.W.: Measurement of endogenous estrogens: analytical challenges and recent advances. J. Chromatogr. A. 1000, 401–412 (2003)CrossRefGoogle Scholar
  11. 11.
    Kanu, A.B., Dwivedi, P., Tam, M., Matz, L., Hill Jr., H.H.: Ion mobility-mass spectrometry. J. Mass Spectrom. 43, 1–22 (2008)CrossRefGoogle Scholar
  12. 12.
    Cumeras, R., Figueras, E., Davis, C.E., Baumbach, J.I., Gracia, I.: Review on ion mobility spectrometry. Part 1: current instrumentation. Analyst. 140, 1376–1390 (2015)CrossRefGoogle Scholar
  13. 13.
    Nozaki, O.: Steroid analysis for medical diagnosis. J. Chromatogr. A. 935, 267–278 (2001)CrossRefGoogle Scholar
  14. 14.
    Lewis, J.: Steroid analysis in saliva: an overview. Clin. Biochem. Rev. 27, 139–146 (2006)Google Scholar
  15. 15.
    Kolakowski, B.M., Mester, Z.: Review of applications of high-field asymmetric waveform ion mobility spectrometry (FAIMS) and differential mobility spectrometry (DMS). Analyst. 132, 842–864 (2007)CrossRefGoogle Scholar
  16. 16.
    Kaur-Atwal, G., Reynolds, J.C., Mussell, C., Champarnaud, E., Knapman, T.W., Ashcroft, A.E., O'Connor, G., Christie, S.D., Creaser, C.S.: Determination of testosterone and epitestosterone glucuronides in urine by ultra performance liquid chromatography-ion mobility-mass spectrometry. Analyst. 136, 3911–3916 (2011)CrossRefGoogle Scholar
  17. 17.
    Van Renterghem, P., Van Eenoo, P., Sottas, P.E., Saugy, M., Delbeke, F.: A pilot study on subject-based comprehensive steroid profiling: novel biomarkers to detect testosterone misuse in sports. Clin. Endocrinol. 75, 134–140 (2011)CrossRefGoogle Scholar
  18. 18.
    Lapthorn, C., Pullen, F., Chowdhry, B.Z.: Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: separating and assigning structures to ions. Mass Spectrom. Rev. 32, 43–71 (2013)CrossRefGoogle Scholar
  19. 19.
    Ahonen, L., Fasciotti, M., Gennas, G.B., Kotiaho, T., Daroda, R.J., Eberlin, M., Kostiainen, R.: Separation of steroid isomers by ion mobility mass spectrometry. J. Chromatogr. A. 1310, 133–137 (2013)CrossRefGoogle Scholar
  20. 20.
    Chouinard, C.D., Beekman, C.R., Kemperman, R.H.J., King, H.M., Yost, R.A.: Ion mobility-mass spectrometry separation of steroid structural isomers and epimers. Int. J. Ion Mobil. Spectrom. 20, 31–39 (2017)CrossRefGoogle Scholar
  21. 21.
    Chouinard, C.D., Cruzeiro, V.W., Roitberg, A.E., Yost, R.A.: Experimental and theoretical investigation of sodiated multimers of steroid epimers with ion mobility-mass spectrometry. J. Am. Soc. Mass Spectrom. 28, 323–331 (2017)CrossRefGoogle Scholar
  22. 22.
    Shvartsburg, A.A., Smith, R.D.: Fundamentals of traveling wave ion mobility spectrometry. Anal. Chem. 80, 9689–9699 (2008)CrossRefGoogle Scholar
  23. 23.
    Giles, K., Williams, J.P., Campuzano, I.: Enhancements in travelling wave ion mobility resolution. Rapid Commun. Mass Spectrom. 25, 1559–1566 (2011)CrossRefGoogle Scholar
  24. 24.
    Henderson, S.C., Li, J., Countermann, A.E., Clemmer, D.E.: Intrinsic size parameters for Val, Ile, Leu, Gln, Thr, Phe, and Trp residues from ion mobility measurements of polyamino acid ions. J. Phys. Chem. B. 103, 8780–8785 (1999)CrossRefGoogle Scholar
  25. 25.
    Bush, M.F., Campuzano, I.D., Robinson, C.V.: Ion mobility mass spectrometry of peptide ions: effects of drift gas and calibration strategies. Anal. Chem. 84, 7124–7130 (2012)CrossRefGoogle Scholar
  26. 26.
    Campuzano, I., Bush, M.F., Robinson, C.V., Beaumont, C., Richardson, K., Kim, H., Kim, H.I.: Structural characterization of drug-like compounds by ion mobility mass spectrometry: comparison of theoretical and experimentally derived nitrogen collision cross sections. Anal. Chem. 84, 1026–1033 (2012)CrossRefGoogle Scholar
  27. 27.
    Pagel, K., Harvey, D.J.: Ion mobility-mass spectrometry of complex carbohydrates: collision cross sections of sodiated N-linked glycans. Anal. Chem. 85, 5138–5145 (2013)CrossRefGoogle Scholar
  28. 28.
    Hofmann, J., Struwe, W.B., Scarff, C.A., Scrivens, J.H., Harvey, D.J., Pagel, K.: Estimating collision cross sections of negatively charged N-glycans using traveling wave ion mobility-mass spectrometry. Anal. Chem. 86, 10789–10795 (2014)CrossRefGoogle Scholar
  29. 29.
    Paglia, G., Williams, J.P., Menikarachchi, L., Thompson, J.W., Tyldesley-Worster, R., Halldorsson, S., Rolfsson, O., Moseley, A., Grant, D., Langridge, J., Palsson, B.O., Astarita, G.: Ion mobility derived collision cross sections to support metabolomics applications. Anal. Chem. 86, 3985–3993 (2014)CrossRefGoogle Scholar
  30. 30.
    Forsythe, J.G., Petrov, A.S., Walker, C.A., Allen, S.J., Pellissier, J.S., Bush, M.F., Hud, N.V., Fernandez, F.M.: Collision cross section calibrants for negative ion mode traveling wave ion mobility-mass spectrometry. Analyst. 140, 6853–6861 (2015)CrossRefGoogle Scholar
  31. 31.
    Hines, K.M., May, J.C., McLean, J.A., Xu, L.: Evaluation of collision cross section calibrants for structural analysis of lipids by traveling wave ion mobility-mass spectrometry. Anal. Chem. 88, 7329–7336 (2016)CrossRefGoogle Scholar
  32. 32.
    Zheng, X., Aly, N.A., Zhou, Y., Dupuis, K.T., Bilbao, A., Paurus, V.L., Orton, D.J., Wilson, R., Payne, S.H., Smith, R.D., Baker, E.S.: A structural examination and collision cross section database for over 500 metabolites and xenobiotics using drift tube ion mobility spectrometry. Chem. Sci. 8, 7724–2236 (2017)Google Scholar
  33. 33.
    Ruotolo, B.T., Benesch, J.L., Sandercock, A.M., Hyung, S.J., Robinson, C.V.: Ion mobility-mass spectrometry analysis of large protein complexes. Nat. Protoc. 3, 1139–1152 (2008)CrossRefGoogle Scholar
  34. 34.
    Thalassinos, K., Grabenauer, M., Slade, S.E., Hilton, G.R., Bowers, M.T., Scrivens, J.H.: Characterization of phosphorylated peptides using traveling wave-based and drift cell ion mobility mass spectrometry. Anal. Chem. 81, 248–254 (2008)CrossRefGoogle Scholar
  35. 35.
    Smith, D., Knapman, T., Campuzano, I., Malham, R., Berryman, J., Radford, S., Ashcroft, A.: Deciphering drift time measurements from travelling wave ion mobility spectrometry-mass spectrometry studies. Eur. J. Mass Spectrom. 15, 113–130 (2009)CrossRefGoogle Scholar
  36. 36.
    Huang, Y., Dodds, E.D.: Ion mobility studies of carbohydrates as group I adducts: isomer specific collisional cross section dependence on metal ion radius. Anal. Chem. 85, 9728–9735 (2013)CrossRefGoogle Scholar
  37. 37.
    Gelb, A.S., Jarratt, R.E., Huang, Y., Dodds, E.D.: A study of calibrant selection in measurement of carbohydrate and peptide ion-neutral collision cross sections by traveling wave ion mobility spectrometry. Anal. Chem. 86, 11396–11402 (2014)CrossRefGoogle Scholar
  38. 38.
    Hudgins, R.R., Ratner, M.A., Jarrold, M.F.: Design of helices that are stable in Vacuo. J. Am. Chem. Soc. 120, 12974–12975 (1998)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Nebraska - LincolnLincolnUSA
  2. 2.Department of Chemistry and BiochemistrySpelman CollegeAtlantaUSA

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