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)

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.

Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food

“…The mobile phase(s) was also composed of acetic acid, formic acid, ammonium formate and/or ammonia (Andrýs et al, 2015;Christensen et al, 2012;Jiang et al, 2013;Lage et al, 2014;McCarron et al, 2014).…”

“…The derivatization procedures rely on the use of either ACQ (Andrýs et al, 2015;Christensen et al, 2012;Faassen et al, 2012;Lage et al, 2014;McCarron et al, 2014) or N-hydroxysuccinimide ester of N-butylnicotinic acid (C 4 -NA-NHS) (Andrýs et al, 2015) as derivatizing agent. The precursor ion monitored for the presence of BMAA in positive ionization mode is either m/z 119 for the underivatized form or m/z 221 (BMAA-C4-NA) and m/z 459 (BMAA-ACQ) for the derivatized form of the toxin.…”

“…LC-MS/MS analyses can be performed on derivatized (Andrýs et al, 2015;Christensen et al, 2012;Faassen et al, 2012;Jiang et al, 2013;Lage et al, 2014;McCarron et al, 2014) or underivatized extracts (Faassen et al, 2012;Reveillon et al, 2014;Rosen and Hellenas, 2008) obtained from different matrices (BGAS, cycad plants, shellfish…). The derivatization procedures rely on the use of either ACQ (Andrýs et al, 2015;Christensen et al, 2012;Faassen et al, 2012;Lage et al, 2014;McCarron et al, 2014) or N-hydroxysuccinimide ester of N-butylnicotinic acid (C 4 -NA-NHS) (Andrýs et al, 2015) as derivatizing agent.…”

“…Separation prior to LC-MS/MS analysis was carried out on columns of different nature: C18 (Andrýs et al, 2015;Christensen et al, 2012;Jiang et al, 2013;Lage et al, 2014;McCarron et al, 2014), ZIC HILIC (Faassen et al, 2012;Reveillon et al, 2014;Rosen and Hellenas, 2008), TSK gel amide-80 (McCarron et al, 2014), Zorbax Eclipse AAA (Faassen et al, 2012) and sizes.…”

The neurotoxin BMAA in aquatic systems : analysis, occurrence and effects

“…[76,93,103,135]), and is now easier to perform as D 3 BMAA has become commercially available. In addition, possible interferences of structural isomers are investigated [97,104], and new methods of separation are explored [104,202], as are alternative derivatisation techniques [203].…”