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Selective quantitation of the neurotoxin BMAA by use of hydrophilic-interaction liquid chromatography–differential mobility spectrometry–tandem mass spectrometry (HILIC–DMS–MS/MS)

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Abstract

The neurotoxin β-N-methylamino-l-alanine (BMAA) has been reported in cyanobacteria and shellfish, raising concerns about widespread human exposure. However, inconsistent results for BMAA analysis have led to controversy. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) is the most appropriate method for analysis of BMAA, but the risk of interference from isomers, other sample components, and the electrospray background is still present. We have investigated differential mobility spectrometry (DMS) as an ion filter to improve selectivity in the hydrophilic interaction liquid chromatographic (HILIC)–MS/MS determination of BMAA. We obtained standards for two BMAA isomers not previously analyzed by HILIC–MS, β-amino-N-methylalanine and 3,4-diaminobutanoic acid, and the typically used 2,4-diaminobutanoic acid and N-(2-aminoethyl)glycine. DMS separation of BMAA from these isomers was achieved and optimized conditions were used to develop a sensitive and highly selective multidimensional HILIC–DMS–MS/MS method. This work revealed current technical limitations of DMS for trace quantitation, and practical solutions were implemented. Accurate control of low levels of DMS carrier gas modifier was essential, but required external metering. The linearity of our optimized method was excellent from 0.01 to 6 μmol L−1. The instrumental LOD was 0.4 pg BMAA injected on-column and the estimated method LOD was 20 ng g−1 dry weight for BMAA in sample matrix. The method was used to analyze cycad plant tissue, a cyanobacterial reference material, and mussel tissues, by use of isotope-dilution quantitation with deuterated BMAA. This confirmed the presence of BMAA and several of its isomers in cycad and mussel tissues, including commercially available mussel tissue reference materials certified for other biotoxins.

Differential Mobility Spectrometry is used to increases the selectivity of BMAA analysis by HILIC–MS/MS

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References

  1. Vega A, Bell EA (1967) Phytochemistry 6:759–762

    Article  CAS  Google Scholar 

  2. Bradley WG, Borenstein AR, Nelson LM, Codd GA, Rosen BH, Stommel EW, Cox PA (2013) Amyotroph Lateral Scler Frontotemporal Degener 14:325–333

  3. Chiu AS, Gehringer MM, Welch JH, Neilan BA (2011) Int J Environ Res Public Health 8:3728–3746

    Article  CAS  Google Scholar 

  4. Banack SA, Caller T, Henegan P, Haney J, Murby A, Metcalf JS, Powell J, Cox PA, Stommel E (2015) Toxins 7:322–336

    Article  CAS  Google Scholar 

  5. Banack SA, Metcalf JS, Bradley WG, Cox PA (2014) Toxicon 90:167–173

    Article  CAS  Google Scholar 

  6. Cox PA, Banack SA, Murch SJ (2003) Proc Natl Acad Sci U S A 100:13380–13383

    Article  CAS  Google Scholar 

  7. Faassen EJ, Gillissen F, Lürling M (2012) PLoS One 7:e36667

    Article  CAS  Google Scholar 

  8. Faassen EJ (2014) Toxins 6:1109–1138

    Article  Google Scholar 

  9. Kruger T, Oelmuller R, Luckas BJ (2012) Endocytobiosis Cell Res 22:29–36

    Google Scholar 

  10. Jiang L, Aigret B, Borggraeve W, Spacil Z, Ilag L (2012) Anal Bioanal Chem 403:1719–1730

    Article  CAS  Google Scholar 

  11. Salomonsson ML, Hansson A, Bondesson U (2013) Anal Methods 5:4865–4874

    Article  Google Scholar 

  12. Jiang L, Kiselova N, Rosen J, Ilag LL (2014) Sci Rep 6931:1–7

    Google Scholar 

  13. McCarron P, Logan AC, Giddings SD, Quilliam MA (2014) Aquat Biosyst 10(5):1–7

    Google Scholar 

  14. Li AF, Fan H, Ma FF, McCarron P, Thomas K, Tang XH, Quilliam MA (2012) Analyst 137:1210–1219

    Article  CAS  Google Scholar 

  15. Réveillon D, Abadie E, Séchet V, Brient L, Savar V, Bardouil M, Hess P, Amzil Z (2014) Mar Drugs 12:5441–5467

    Article  Google Scholar 

  16. Combes A, El Abdellaoui S, Sarazin C, Vial J, Mejean A, Ploux O, Pichon V (2013) Anal Chim Acta 771:42–49

    Article  CAS  Google Scholar 

  17. Marler TE, Snyder LR, Shaw CA (2010) Toxicon 56:563–568

    Article  CAS  Google Scholar 

  18. Guevremont R, Purves RW, Barnett DA, Ells B (2006) FAIMS apparatus and method using carrier gases that contain a trace amount of a dopant species. US Patent no. 7,026,612

  19. Shvartsburg AA (2009) Differential Ion Mobility Spectrometry. CRC Press, Boca Raton

    Google Scholar 

  20. Schneider BB, Nazarov EG, Londry F, Vouros P, Covey TR (2015) Mass Spectrom Rev in press doi:10.1002/mas.21453

  21. Campbell JL, Zhu M, Hopkins WS (2014) J Am Soc Mass Spectrom 25:1583–1591

    Article  CAS  Google Scholar 

  22. Kapron JT, Jemal M, Duncan G, Kolakowski B, Purves R (2005) Rapid Commun Mass Spectrom 19:1979–1983

    Article  CAS  Google Scholar 

  23. Guevremont R, Kloakowski B (2005) Am Lab 37:11–14

    CAS  Google Scholar 

  24. Klaassen T, Szwandt S, Kapron JT, Roemer A (2009) Rapid Commun Mass Spectrom 23:2301–2306

    Article  CAS  Google Scholar 

  25. Prasad S, Belford M, Dunyach J, Purves RJ (2014) Am Soc Mass Spectrom 25:2143–2153

    Article  CAS  Google Scholar 

  26. Jin W, Jarvis M, Star-Weinstock M, Altemus M (2013) Anal Bioanal Chem 405:9497–9508

    Article  CAS  Google Scholar 

  27. Ray JA, Kushnir MM, Yost RA, Rockwood AL, Meikle AW (2015) Performance enhancement in the measurement of 5 endogenous steroids in human serum by LC–MS/MS combined with differential ion mobility spectrometry. Clin Chim Acta 438:330–336

  28. Purves RW, Ozog A, Ambrose SJ, Prasad S, Belford M, Dunyach J-J (2014) J Am Soc Mass Spectrom 25:1274–1284

    Article  CAS  Google Scholar 

  29. Pang N, Yan C (2014) Int J Mass Spectrom 362:48–55

    Article  CAS  Google Scholar 

  30. Beach DG, Melanson JE, Purves RW (2015) Anal Bioanal Chem 407:2473–2484

    Article  CAS  Google Scholar 

  31. Burton IW, Quilliam MA, Walter JA (2005) Anal Chem 77:3123–3131

    Article  CAS  Google Scholar 

  32. Hollingdale K, Thomas K, Lewis N, Békri K, McCarron P, Quilliam MA (2015) Anal Bioanal Chem 407:5353–5363

    Article  CAS  Google Scholar 

  33. Beach DG, Gabryelski W (2012) J Am Soc Mass Spectrom 23:858–868

    Article  CAS  Google Scholar 

  34. Kolakowski BM, McCooeye MA, Mester Z (2006) Rapid Commun Mass Spectrom 20:3319–3329

    Article  CAS  Google Scholar 

  35. Schneider BB, Nazarov EG, Londry F, Kang Y, Covey TR (2014) Improved DMS Performance with a Jet Injector Inlet. 62nd ASMS Conference on Mass Spectrometry and Allied Topics, Baltimore, MD

  36. Pagliano E, Mester Z, Meija J (2013) Anal Bioanal Chem 405:2879–2887

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Randy Purves, for input on modifications to enable the introduction of low levels of gas modifiers and for helpful discussions, Sabrina Giddings and Krista Thomas, for technical assistance, and Pearse McCarron for editorial input.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Measurement Science and Standards, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada

    Daniel G. Beach, Elliott S. Kerrin & Michael A. Quilliam

  2. Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada

    Elliott S. Kerrin & Michael A. Quilliam

Authors
  1. Daniel G. Beach
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  2. Elliott S. Kerrin
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  3. Michael A. Quilliam
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Correspondence to Daniel G. Beach.

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Beach, D.G., Kerrin, E.S. & Quilliam, M.A. Selective quantitation of the neurotoxin BMAA by use of hydrophilic-interaction liquid chromatography–differential mobility spectrometry–tandem mass spectrometry (HILIC–DMS–MS/MS). Anal Bioanal Chem 407, 8397–8409 (2015). https://doi.org/10.1007/s00216-015-9012-8

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  • DOI: https://doi.org/10.1007/s00216-015-9012-8

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