title: Selective quantitation of the neurotoxin BMAA by use of hydrophilic-interaction liquid chromatography-differential mobility spectrometry-tandem mass spectrometry (HILIC-DMS-MS/MS).
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. Graphical Abstract Differential Mobility Spectrometry is used to increases the selectivity of BMAA analysis by HILIC-MS/MS.
authors.affiliation: Measurement Science and Standards, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada. daniel.beach@nrc-cnrc.gc.ca.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Beach
authors.affiliation: Measurement Science and Standards, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada.|Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada.
authors.forename: Elliott S
authors.initials: ES
authors.lastname: Kerrin
authors.affiliation: Measurement Science and Standards, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada.|Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, NS, B3H 4R2, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quilliam
mesh_terms: D000599:Amino Acids, Diamino / Q000032:analysis*; D000613:Aminobutyrates / Q000032:analysis; D000818:Animals; D049872:Bivalvia / Q000737:chemistry / Q000378:metabolism; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards*; D000458:Cyanobacteria / Q000737:chemistry / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D029784:Cycas / Q000737:chemistry / Q000378:metabolism; D005506:Food Contamination; D005998:Glycine / Q000031:analogs & derivatives / Q000032:analysis; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D009498:Neurotoxins / Q000032:analysis*; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*
chemical_list: C474938:3,4-diaminobutanoic acid; D000599:Amino Acids, Diamino; D000613:Aminobutyrates; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; C028791:N-(2-aminoethyl)glycine; D005998:Glycine
keywords: BMAA; Cyanotoxin; DMS; FAIMS; Ion mobility; Marine toxins; Reference materials