Advertisement

Analytical and Bioanalytical Chemistry

, Volume 407, Issue 13, pp 3743–3750 | Cite as

Improved detection of β-N-methylamino-l-alanine using N-hydroxysuccinimide ester of N-butylnicotinic acid for the localization of BMAA in blue mussels (Mytilus edulis)

  • Rudolf Andrýs
  • Javier Zurita
  • Nadezda Zguna
  • Klaas Verschueren
  • Wim M. De Borggraeve
  • Leopold L. Ilag
Research Paper

Abstract

β-N-Methylamino-l-alanine (BMAA) is an important non-protein amino acid linked to neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS). Because it can be transferred and bioaccumulated higher up the food chain, it poses significant public health concerns; thus, improved detection methods are of prime importance for the identification and management of these toxins. Here, we report the successful use of N-hydroxysuccinimide ester of N-butylnicotinic acid (C4-NA-NHS) for the efficient separation of BMAA from its isomers and higher sensitivity in detecting BMAA compared to the current method of choice using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization. Implementation of this efficient method allowed localization of BMAA in the non-visceral tissues of blue mussels, suggesting that more efficient depuration may be required to remove this toxin prior to consumption. This is a crucial method in establishing the absence or presence of the neurotoxic amino acid BMAA in food, environmental or biomedical samples.

Keywords

BMAA Isomers Neurotoxin LC-MS/MS Improved derivatization Quaternary ammonium 

Notes

Acknowledgments

This project was supported by Charles University (SVV 260 065), European Social Fund and the state budget of the Czech Republic (TEAB) project no. CZ.1.07/2.3.00/20.0235 and by project FAFIS no. CZ.1.07/2.2.00/28.0194. We thank Liying Jiang and Ulrika Nilsson for their helpful discussions.

References

  1. 1.
    Cox PA, Banack SA, Murch SJ (2003) Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci U S A 100:13380–13383. doi: 10.1073/pnas.2235808100 CrossRefGoogle Scholar
  2. 2.
    Jiang L, Eriksson J, Lage S, Jonasson S, Shams S, Mehine M, Ilag LL, Rasmussen U (2014) Diatoms: a novel source for the neurotoxin BMAA in aquatic environments. PLoS One 9:e84578. doi: 10.1371/journal.pone.0084578 CrossRefGoogle Scholar
  3. 3.
    Jiang L, Ilag LL (2014) Detection of endogenous BMAA in dinoflagellate (Heterocapsa triquetra) hints at evolutionary conservation and environmental concern. PubRaw Sci 1:1–8Google Scholar
  4. 4.
    Lage S, Costa PR, Moita T, Eriksson J, Rasmussen U, Rydberg SJ (2014) BMAA in shellfish from two Portuguese transitional water bodies suggests the marine dinoflagellate Gymnodinium catenatum as a potential BMAA source. Aquat Toxicol 152:131–138. doi: 10.1016/j.aquatox.2014.03.029 CrossRefGoogle Scholar
  5. 5.
    Dunlop RA, Cox PA, Banack SA, Rodgers KJ (2013) The non-protein amino acid BMAA is misincorporated into human proteins in place of l-serine causing protein misfolding and aggregation. PLoS One 8:e75376. doi: 10.1371/journal.pone.0075376 CrossRefGoogle Scholar
  6. 6.
    Glover WB, Mash DC, Murch SJ (2014) The natural non-protein amino acid N-β-methylamino-l-alanine (BMAA) is incorporated into protein during synthesis. Amino Acids 46:2553–2559. doi: 10.1007/s00726-014-1812-1 CrossRefGoogle Scholar
  7. 7.
    Field NC, Metcalf JS, Caller TA, Banack SA, Cox PA, Stommel EW (2013) Linking β-methylamino-l-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD. Toxicon 70:179–183. doi: 10.1016/j.toxicon.2013.04.010 CrossRefGoogle Scholar
  8. 8.
    Banack SA, Metcalf JS, Bradley WG, Cox PA (2014) Detection of cyanobacterial neurotoxin β-N-methylamino-l-alanine within shellfish in the diet of an ALS patient in Florida. Toxicon 90:167–173. doi: 10.1016/j.toxicon.2014.07.018 CrossRefGoogle Scholar
  9. 9.
    Jiang L, Kiselova N, Rosén J, Ilag LL (2014) Quantification of neurotoxin BMAA (β-N-methylamino-l-alanine) in seafoods from Swedish markets. Nat Sci Reports. doi: 10.1038/srep06931 Google Scholar
  10. 10.
    Faassen EJ (2014) Presence of the neurotoxin BMAA in aquatic ecosystems: what do we really know? Toxins (Basel) 6:1109–1138. doi: 10.3390/toxins6031109 CrossRefGoogle Scholar
  11. 11.
    Cohen SA (2012) Analytical techniques for the detection of α-amino-β-methylaminopropionic acid. Analyst 137:1991–2005. doi: 10.1039/c2an16250d CrossRefGoogle Scholar
  12. 12.
    Faassen EJ, Gillissen F, Zweers HAJ, Lürling M (2009) Determination of the neurotoxins BMAA (β-N-methylamino-l-alanine) and DAB (α-,γ-diaminobutyric acid) by LC-MSMS in Dutch urban waters with cyanobacterial blooms. Amyotroph Lateral Scler 10:79–84CrossRefGoogle Scholar
  13. 13.
    Combes A, El Abdellaoui S, Sarazin C, Vial J, Mejean A, Ploux O, Pichon V (2013) Validation of the analytical procedure for the determination of the neurotoxin β-N-methylamino-l-alanine in complex environmental samples. Anal Chim Acta 771:42–49. doi: 10.1016/j.aca.2013.02.016 CrossRefGoogle Scholar
  14. 14.
    McCarron P, Logan AC, Giddings SD, Quilliam MA (2014) Analysis of β-N-methylamino-l-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry. Aquat Biosyst 10:5. doi: 10.1186/2046-9063-10-5 CrossRefGoogle Scholar
  15. 15.
    Spáčil Z, Eriksson J, Jonasson S, Rasmussen U, Ilag LL, Bergman B (2010) Analytical protocol for identification of BMAA and DAB in biological samples. Analyst 135:127–132. doi: 10.1039/b921048b CrossRefGoogle Scholar
  16. 16.
    Yang W-C, Mirzaei H, Liu X, Regnier FE (2006) Enhancement of amino acid detection and quantification by electrospray ionization mass spectrometry. Anal Chem 78:4702–4708. doi: 10.1021/ac0600510 CrossRefGoogle Scholar
  17. 17.
    Jiang L, Aigret B, De Borggraeve WM, Spacil Z, Ilag LL (2012) Selective LC-MS/MS method for the identification of BMAA from its isomers in biological samples. Anal Bioanal Chem 403:1719–1730. doi: 10.1007/s00216-012-5966-y CrossRefGoogle Scholar
  18. 18.
    Cox PA, Banack SA, Murch SJ, Rasmussen U, Tien G, Bidigare RR, Metcalf JS, Morrison LF, Codd GA, Bergman B (2005) Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid. Proc Natl Acad Sci U S A 102:5074–5078. doi: 10.1073/pnas.0501526102 CrossRefGoogle Scholar
  19. 19.
    Rosén J, Hellenäs K-E (2008) Determination of the neurotoxin BMAA (beta-N-methylamino-l-alanine) in cycad seed and cyanobacteria by LC-MS/MS (liquid chromatography tandem mass spectrometry). Analyst 133:1785–1789. doi: 10.1039/b809231a CrossRefGoogle Scholar
  20. 20.
    Krüger T, Mönch B, Oppenhäuser S, Luckas B (2010) LC-MS/MS determination of the isomeric neurotoxins BMAA (beta-N-methylamino-l-alanine) and DAB (2,4-diaminobutyric acid) in cyanobacteria and seeds of Cycas revoluta and Lathyrus latifolius. Toxicon 55:547–557. doi: 10.1016/j.toxicon.2009.10.009 CrossRefGoogle Scholar
  21. 21.
    Allard E, Tröger RA, Arvidsson B, Sjöberg PJR (2010) Quantitative aspects of analyzing small molecules—monitoring singly or doubly charged ions? A case study of ximelagatran. Rapid Commun Mass Spectrom 24:429–435. doi: 10.1002/rcm.4414 CrossRefGoogle Scholar
  22. 22.
    Shimbo K, Yahashi A, Hirayama K, Nakazawa M, Miyano H (2009) Multifunctional and highly sensitive precolumn reagents for amino acids in liquid chromatography/tandem mass spectrometry. Anal Chem 81:5172–5179. doi: 10.1021/ac900470w CrossRefGoogle Scholar
  23. 23.
    Inagaki S, Tano Y, Yamakata Y, Higashi T, Min JZ, Toyo’oka T (2010) Highly sensitive and positively charged precolumn derivatization reagent for amines and amino acids in liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 24:1358–1364. doi: 10.1002/rcm.4521 CrossRefGoogle Scholar
  24. 24.
    Crick PJ, Aponte J, Bentley TW, Matthews I, Wang Y, Griffiths WJ (2014) Evaluation of novel derivatisation reagents for the analysis of oxysterols. Biochem Biophys Res Commun 446:756–761. doi: 10.1016/j.bbrc.2014.01.173 CrossRefGoogle Scholar
  25. 25.
    Metcalf JS, Banack SA, Lindsay J, Morrison LF, Cox PA, Codd GA (2008) Co-occurrence of beta-N-methylamino-l-alanine, a neurotoxic amino acid with other cyanobacterial toxins in British waterbodies, 1990-2004. Environ Microbiol 10:702–708. doi: 10.1111/j.1462-2920.2007.01492.x CrossRefGoogle Scholar
  26. 26.
    Mazzella N, Delmas F, Delest B, Méchin B, Madigou C, Allenou J-P, Gabellec R, Caquet T (2009) Investigation of the matrix effects on a HPLC-ESI-MS/MS method and application for monitoring triazine, phenylurea and chloroacetanilide concentrations in fresh and estuarine waters. J Environ Monit 11:108–115. doi: 10.1039/b805160g CrossRefGoogle Scholar
  27. 27.
    Rebane R, Oldekop M-L, Herodes K (2014) Matrix influence on derivatization and ionization processes during selenoamino acid liquid chromatography electrospray ionization mass spectrometric analysis. J Chromatogr B Analyt Technol Biomed Life Sci 955–956:34–41. doi: 10.1016/j.jchromb.2014.02.016 CrossRefGoogle Scholar
  28. 28.
    Jiang L, Johnston E, Aberg KM, Nilsson U, Ilag LL (2013) Strategy for quantifying trace levels of BMAA in cyanobacteria by LC/MS/MS. Anal Bioanal Chem 405:1283–1292. doi: 10.1007/s00216-012-6550-1 CrossRefGoogle Scholar
  29. 29.
    Mafra LL, Bricelj VM, Fennel K (2010) Domoic acid uptake and elimination kinetics in oysters and mussels in relation to body size and anatomical distribution of toxin. Aquat Toxicol 100:17–29. doi: 10.1016/j.aquatox.2010.07.002 CrossRefGoogle Scholar
  30. 30.
    Karlsson O, Jiang L, Andersson M, Ilag LL, Brittebo EB (2014) Protein association of the neurotoxin and non-protein amino acid BMAA (β-N-methylamino-l-alanine) in the liver and brain following neonatal administration in rats. Toxicol Lett 226:1–5. doi: 10.1016/j.toxlet.2014.01.027 CrossRefGoogle Scholar
  31. 31.
    Peña-Llopis S, Serrano R, Pitarch E, Beltrán E, Ibáñez M, Hernández F, Peña JB (2014) N-Acetylcysteine boosts xenobiotic detoxification in shellfish. Aquat Toxicol 154:131–140. doi: 10.1016/j.aquatox.2014.05.006 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Rudolf Andrýs
    • 1
    • 2
  • Javier Zurita
    • 1
  • Nadezda Zguna
    • 1
  • Klaas Verschueren
    • 3
  • Wim M. De Borggraeve
    • 3
  • Leopold L. Ilag
    • 1
  1. 1.Department of Environmental Science and Analytical ChemistryStockholm UniversityStockholmSweden
  2. 2.Department of Biochemical SciencesFaculty of Pharmacy of Charles UniversityHradec KrálovéCzech Republic
  3. 3.Department of ChemistryUniversity of LeuvenHeverleeBelgium

Personalised recommendations