A Single Laboratory Validation for the Analysis of Underivatized β-N-Methylamino-L-Alanine (BMAA)

Tymm, Fiona J. M.; Bishop, Stephanie L.; Murch, Susan J.

doi:10.1007/s12640-019-00137-4

Cited by 13 publications

(12 citation statements)

References 63 publications

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“…We note that BMAA and BAMA are widely separated by retention times using AQC derivatization (Banack 2020). The m/z transition 119 > 102 in underivatized methods has shown inconsistent results in the literature (Baker et al 2018;Beach et al 2018;Li et al 2018;Tymm et al 2019). Authors have used additional ion separation steps, such as differential mobility spectrometry (DMS), which acts as an ion filter by separating ions in a matrix based on their mobility in high or low electrical field strength, to adequately separate BMAA from BAMA but this requires a skilled analyst (Beach et al 2015(Beach et al , 2018.…”

Section: Planktonmentioning

confidence: 79%

“…We note a recent publication on BMAA within flying fox tissues published since the Chernoff et al (2017) review (in which Chernoff is a co-author) failed to find BMAA in these tissues (Foss et al 2018). This attempt to analyze flying fox tissue for BMAA used a ZIC®-HILIC column which, as previously mentioned, has been shown to be unreliable and not fit for the purpose of BMAA analysis in biological matrices (Foss et al 2018;Tymm et al 2019). Foss et al (2018) reported co-elution of BMAA and BAMA using that method and reported a wide range of spike recoveries for total BMAA analysis in flying fox tissues using hydrolysis and SPE (68 ± 21%), further indicating that the method used is not fit for the matrix analyzed.…”

Section: Misrepresentation Of the Flying Fox Hypothesismentioning

confidence: 99%

“…The increased molecular weight of derivatized BMAA facilitates identification of the precursor and product ions by MS/MS, leading to higher sensitivity, and RPLC columns are generally more robust than HILIC columns (Faassen et al 2016;Yan et al 2017). Certain HILIC columns tend to have a short lifetime which can result in a loss of signal of up to 100% over a 6-week period, resulting in extremely low recoveries and inaccurate and imprecise results (Tymm et al 2019). It is noteworthy that an attempt to validate the analysis of BMAA using a ZIC®-HILIC column in a cyanobacterial matrix failed to meet AOAC™ guideline criteria in "selectivity, accuracy, precision, repeatability, and demonstrated poor sensitivity and lack of ruggedness during chromatographic runs" (Tymm et al 2019).…”

Section: Planktonmentioning

confidence: 99%

“…Certain HILIC columns tend to have a short lifetime which can result in a loss of signal of up to 100% over a 6-week period, resulting in extremely low recoveries and inaccurate and imprecise results (Tymm et al 2019). It is noteworthy that an attempt to validate the analysis of BMAA using a ZIC®-HILIC column in a cyanobacterial matrix failed to meet AOAC™ guideline criteria in "selectivity, accuracy, precision, repeatability, and demonstrated poor sensitivity and lack of ruggedness during chromatographic runs" (Tymm et al 2019). This study concluded that "analysis of a cyanobacterial matrix for BMAA using a ZIC®-HILIC column is not fit for purpose" and therefore "not suitable for detection or quantification of BMAA or its isomers in cyanobacteria or other related biological matrices" (Tymm et al 2019).…”

Section: Planktonmentioning

confidence: 99%

“…It is noteworthy that an attempt to validate the analysis of BMAA using a ZIC®-HILIC column in a cyanobacterial matrix failed to meet AOAC™ guideline criteria in "selectivity, accuracy, precision, repeatability, and demonstrated poor sensitivity and lack of ruggedness during chromatographic runs" (Tymm et al 2019). This study concluded that "analysis of a cyanobacterial matrix for BMAA using a ZIC®-HILIC column is not fit for purpose" and therefore "not suitable for detection or quantification of BMAA or its isomers in cyanobacteria or other related biological matrices" (Tymm et al 2019). Furthermore, the quantification of BMAA using RPLC and AQC derivatization requires careful attention to total amino acid concentrations to ensure a complete derivatization reaction.…”

Section: Planktonmentioning

confidence: 99%

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Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? A Response to a Critical Review of the BMAA Hypothesis

Dunlop

et al. 2021

Neurotox Res

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In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to β-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer’s disease, Parkinson’s disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review’s title which incorrectly refers to BMAA as a “non-essential” amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.

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