Overview of the potent cyanobacterial neurotoxin ß-methylamino-L-alanine (BMAA) and its analytical determination.

Blue-green algae are responsible for the production of different types of toxins which can be neurotoxic, hepatotoxic, cytotoxic and dermatotoxic and that can affect both aquatic and terrestrial life. Since its discovery the neurotoxin ß-methylamino-L-alanine (BMAA) has been a cause for concern, being associated with the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC). The initial focus was on Guam where it was observed that a high number of people were affected by the ALS/PDC complex. Subsequently, researchers were surprised to find levels of BMAA in post mortem brains from Canadian patients who also suffered from ALS/PDC. Recent research demonstrates that BMAA has been found at different levels in the aquatic food web in the brackish waters of the Baltic Sea. There is emerging evidence to suggest that sand-borne algae from Qatar can also contain BMAA. Furthermore, there is now concern because BMAA has been found not only in warmer regions of the world but also in temperate regions like Europe. The aim of this review is to focus on the methods of extraction and analysis of the neurotoxic non-protein amino acid BMAA. We also consider the neurotoxicity, aetiology, and diverse sources and routes of exposure to BMAA. In recent years, different methods have been developed for the analysis of BMAA. Some of these use HPLC-FD, UPLC-UV, UPLC-MS and LC-MS/MS using samples that have been derivatised or underivatised. To date the LC-MS/MS approach is the most widely used analytical technique as it is the most selective and sensitive method for BMAA determination.

A Collaborative Evaluation of LC-MS/MS Based Methods for BMAA Analysis: Soluble Bound BMAA Found to Be an Important Fraction.

Exposure to ß-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of various analytical methods currently employed is rarely compared. A CYANOCOST initiated workshop was organized aimed at training scientists in BMAA analysis, creating mutual understanding and paving the way towards interlaboratory comparison exercises. During this workshop, we tested different methods (extraction followed by derivatization and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis, or directly followed by LC-MS/MS analysis) for trueness and intermediate precision. We adapted three workup methods for the underivatized analysis of animal, brain and cyanobacterial samples. Based on recovery of the internal standard D3BMAA, the underivatized methods were accurate (mean recovery 80%) and precise (mean relative standard deviation 10%), except for the cyanobacterium Leptolyngbya. However, total BMAA concentrations in the positive controls (cycad seeds) showed higher variation (relative standard deviation 21%-32%), implying that D3BMAA was not a good indicator for the release of BMAA from bound forms. Significant losses occurred during workup for the derivatized method, resulting in low recovery (<10%). Most BMAA was found in a trichloroacetic acid soluble, bound form and we recommend including this fraction during analysis.