Epimers of azaspiracids: Isolation, structural elucidation, relative LC-MS response, and in vitro toxicity of 37-epi-azaspiracid-1

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DOIResolve DOI: http://doi.org/10.1021/tx400434b
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TypeArticle
Journal titleChemical Research in Toxicology
ISSN1520-5010
Volume27
Issue4
Pages587600; # of pages: 14
Subject37 epiazaspiracid 1; acetonitrile; azaspiracid; dye; unclassified drug; aqueous solution; article; carbon nuclear magnetic resonance; concentration response; consumer; controlled study; cytotoxicity; cytotoxicity assay; decarboxylation; epimer; epimerization; experimental model; food contamination; half life time; in vitro study; leukemia cell line; liquid chromatography; mass spectrometry; mussel; phytoplankton; proton nuclear magnetic resonance; reaction analysis; sea food; shellfish; structure analysis; tandem mass spectrometry; time; toxicity testing; toxin analysis
AbstractSince azaspiracid-1 (AZA1) was identified in 1998, the number of AZA analogues has increased to over 30. The development of an LC-MS method using a neutral mobile phase led to the discovery of isomers of AZA1, AZA2, and AZA3, present at ∼2-16% of the parent analogues in phytoplankton and shellfish samples. Under acidic mobile phase conditions, isomers and their parents are not separated. Stability studies showed that these isomers were spontaneous epimerization products whose formation is accelerated with the application of heat. The AZA1 isomer was isolated from contaminated shellfish and identified as 37-epi-AZA1 by nuclear magnetic resonance (NMR) spectroscopy and chemical analyses. Similar analysis indicated that the isomers of AZA2 and AZA3 corresponded to 37-epi-AZA2 and 37-epi-AZA3, respectively. The 37-epimers were found to exist in equilibrium with the parent compounds in solution. 37-epi-AZA1 was quantitated by NMR, and relative molar response studies were performed to determine the potential differences in LC-MS response of AZA1 and 37-epi-AZA1. Toxicological effects were determined using Jurkat T lymphocyte cells as an in vitro cell model. Cytotoxicity experiments employing a metabolically based dye (i.e., MTS) indicated that 37-epi-AZA1 elicited a lethal response that was both concentration- and time-dependent, with EC50 values in the subnanomolar range. On the basis of EC50 comparisons, 37-epi-AZA1 was 5.1-fold more potent than AZA1. This data suggests that the presence of these epimers in seafood products should be considered in the analysis of AZAs for regulatory purposes. © 2014 American Chemical Society.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Measurement Science and Standards (MSS-SME)
Peer reviewedYes
NPARC number21272151
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Record identifierd6bab772-25d4-4827-829e-95349dde21c8
Record created2014-07-23
Record modified2016-05-09
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