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Pearse Mccarron - One of the best experts on this subject based on the ideXlab platform.
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a mussel tissue certified reference material for multiple phycotoxins part 5 profiling by liquid chromatography high resolution mass spectrometry
Analytical and Bioanalytical Chemistry, 2021Co-Authors: Elliott J Wright, Pearse MccarronAbstract:A freeze-dried mussel tissue-certified reference material (CRM-FDMT1) was prepared containing the marine algal toxin classes Azaspiracids, okadaic acid and dinophysistoxins, yessotoxins, pectenotoxins, cyclic imines, and domoic acid. Thus far, only a limited number of analogues in CRM-FDMT1 have been assigned certified values; however, the complete toxin profile is significantly more complex. Liquid chromatography-high-resolution mass spectrometry was used to profile CRM-FDMT1. Full-scan data was searched against a list of previously reported toxin analogues, and characteristic product ions extracted from all-ion-fragmentation data were used to guide the extent of toxin profiling. A series of targeted and untargeted acquisition MS/MS experiments were then used to collect spectra for analogues. A number of toxins previously reported in the literature but not readily available as standards were tentatively identified including dihydroxy and carboxyhydroxyyessotoxin, Azaspiracids-33 and -39, sulfonated pectenotoxin analogues, spirolide variants, and fatty acid acyl esters of okadaic acid and pectenotoxins. Previously unreported toxins were also observed including compounds from the pectenotoxin, Azaspiracid, yessotoxin, and spirolide classes. More than one hundred toxin analogues present in CRM-FDMT1 are summarized along with a demonstration of the major acyl ester conjugates of several toxins. Retention index values were assigned for all confirmed or tentatively identified analogues to help with qualitative identification of the broad range of lipophilic toxins present in the material.
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stereochemical definition of the natural product 6r 10r 13r 14r 16r 17r 19s 20s 21r 24s 25s 28s 30s 32r 33r 34r 36s 37s 39r Azaspiracid 3 by total synthesis and comparative analyses
Angewandte Chemie, 2018Co-Authors: Nathaniel T. Kenton, Pearse Mccarron, Antony Akura Okumu, Christopher O Miles, Jane Kilcoyne, Daniel Aduampratwum, Frode Rise, Alistair L Wilkins, Craig J ForsythAbstract:The previously accepted structure of the marine toxin Azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-Azaspiracid-3 chromatographically and spectroscopically matched naturally occurring Azaspiracid-3, whereas the previously assigned 20R epimer did not.
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total synthesis of 6r 10r 13r 14r 16r 17r 19s 20r 21r 24s 25s 28s 30s 32r 33r 34r 36s 37s 39r Azaspiracid 3 reveals non identity with the natural product
Angewandte Chemie, 2018Co-Authors: Nathaniel T. Kenton, Pearse Mccarron, Zhigao Zhang, Yong Chen, Antony Akura Okumu, Jane Kilcoyne, Daniel Aduampratwum, Son Nguyen, Yue Ding, Frode RiseAbstract:A convergent and stereoselective total synthesis of the previously assigned structure of Azaspiracid-3 has been achieved by a late-stage Nozaki-Hiyama-Kishi coupling to form the C21-C22 bond with the C20 configuration unambiguously established from l-(+)-tartaric acid. Postcoupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the resulting C1 primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring Azaspiracid-3 by mass spectrometry, but differed both chromatographically and spectroscopically.
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Selective Extraction and Purification of Azaspiracids from Blue Mussels (Mytilus edulis) Using Boric Acid Gel
2018Co-Authors: Christopher O Miles, Pearse Mccarron, Ingunn A Samdal, Thomas Rundberget, Jane Kilcoyne, Sabrina D. Giddings, Thor Waaler, Kjersti E. LøvbergAbstract:Azaspiracids belong to a family of more than 50 polyether toxins originating from marine dinoflagellates such as Azadinium spinosum. All of the Azaspiracids reported thus far contain a 21,22-dihydroxy group. Boric acid gel can bind selectively to compounds containing vic-diols or α-hydroxycarboxylic acids via formation of reversible boronate complexes. Here we report use of the gel to selectively capture and release Azaspiracids from extracts of blue mussels. Analysis of the extracts and fractions by liquid chromatography–tandem mass spectrometry (LC–MS) showed that this procedure resulted in an excellent cleanup of the Azaspiracids in the extract. Analysis by enzyme-linked immunoasorbent assay (ELISA) and LC–MS indicated that most Azaspiracid analogues were recovered in good yield by this procedure. The capacity of boric acid gel for Azaspiracids was at least 50 μg/g, making this procedure suitable for use in the early stages of preparative purification of Azaspiracids. In addition to its potential for concentration of dilute samples, the extensive cleanup provided by boric acid gel fractionation of Azaspiracids in mussel samples almost eliminated matrix effects during subsequent LC–MS and could be expected to reduce matrix effects during ELISA analysis. The method may therefore prove useful for quantitative analysis of Azaspiracids as part of monitoring programs. Although LC–MS data showed that okadaic acid analogues also bound to the gel, this was much less efficient than for Azaspiracids under the conditions used. The boric acid gel methodology is potentially applicable to other important groups of natural toxins containing diols including ciguatoxins, palytoxins, pectenotoxins, tetrodotoxin, trichothecenes, and toxin glycosides
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Epimers of Azaspiracids: Isolation, Structural Elucidation, Relative LC-MS Response, and in Vitro Toxicity of 37-epi-Azaspiracid‑1
2014Co-Authors: Jane Kilcoyne, Michael A Quilliam, Pearse Mccarron, Frode Rise, Alistair L Wilkins, Michael J. Twiner, Ciara Nulty, Sheila Crain, Christopher O. MilesAbstract:Since 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
Craig J Forsyth - One of the best experts on this subject based on the ideXlab platform.
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synthesis of the c1 c19 domain of Azaspiracid 34
Organic Letters, 2019Co-Authors: Antony A Okumu, Craig J ForsythAbstract:Azaspiracid-34 (AZA34) is a recently described structurally unique member of the Azaspiracid class of marine neurotoxins. Its novel structure, tentatively assigned on the basis of MS and 1H NMR spectroscopy, is accompanied by a 5.5-fold higher level of toxicity against Jurkat T lymphocytes than AZA1. To completely assign the structure of AZA34 and provide material for in-depth biological evaluation and detection, synthetic access to AZA34 was targeted. This began with the convergent and stereoselective assembly of the C1–C19 domain of AZA34 designed to dovetail with the recent total synthesis approach to AZA3.
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Synthesis of the C1–C19 Domain of Azaspiracid-34
2019Co-Authors: Antony A Okumu, Craig J ForsythAbstract:Azaspiracid-34 (AZA34) is a recently described structurally unique member of the Azaspiracid class of marine neurotoxins. Its novel structure, tentatively assigned on the basis of MS and 1H NMR spectroscopy, is accompanied by a 5.5-fold higher level of toxicity against Jurkat T lymphocytes than AZA1. To completely assign the structure of AZA34 and provide material for in-depth biological evaluation and detection, synthetic access to AZA34 was targeted. This began with the convergent and stereoselective assembly of the C1–C19 domain of AZA34 designed to dovetail with the recent total synthesis approach to AZA3
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stereochemical definition of the natural product 6r 10r 13r 14r 16r 17r 19s 20s 21r 24s 25s 28s 30s 32r 33r 34r 36s 37s 39r Azaspiracid 3 by total synthesis and comparative analyses
Angewandte Chemie, 2018Co-Authors: Nathaniel T. Kenton, Pearse Mccarron, Antony Akura Okumu, Christopher O Miles, Jane Kilcoyne, Daniel Aduampratwum, Frode Rise, Alistair L Wilkins, Craig J ForsythAbstract:The previously accepted structure of the marine toxin Azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-Azaspiracid-3 chromatographically and spectroscopically matched naturally occurring Azaspiracid-3, whereas the previously assigned 20R epimer did not.
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Synthesis of the C22–C40 Domain of the Azaspiracids
2016Co-Authors: Zhigao Zhang, Yong Chen, Daniel Adu-ampratwum, Antony Akura Okumu, Nathaniel T. Kenton, Craig J ForsythAbstract:An efficient synthesis of the C22–C40 domain of the Azaspiracids is described. The synthetic route features a Nozaki–Hiyama–Kishi (NHK) coupling and chelation controlled Mukaiyama aldol reaction to access an acyclic intermediate and a double-intramolecular-hetero-Michael addition (DIHMA) to provide the FG-ring system bridged ketal
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synthesis of the c1 c21 domain of Azaspiracids 1 and 3
Organic Letters, 2013Co-Authors: Zhigao Zhang, Yong Chen, Yue Ding, Craig J ForsythAbstract:An efficient synthesis of the C1–C21 fragment of Azaspiracids-1 and −3 is described. This features a Nozaki–Hiyama–Kishi reaction to couple the AB and CD ring precursors and formation of the THF-fused ABCD trioxadispiroketal system under thermodynamic conditions.
Jane Kilcoyne - One of the best experts on this subject based on the ideXlab platform.
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stereochemical definition of the natural product 6r 10r 13r 14r 16r 17r 19s 20s 21r 24s 25s 28s 30s 32r 33r 34r 36s 37s 39r Azaspiracid 3 by total synthesis and comparative analyses
Angewandte Chemie, 2018Co-Authors: Nathaniel T. Kenton, Pearse Mccarron, Antony Akura Okumu, Christopher O Miles, Jane Kilcoyne, Daniel Aduampratwum, Frode Rise, Alistair L Wilkins, Craig J ForsythAbstract:The previously accepted structure of the marine toxin Azaspiracid-3 is revised based upon an original convergent and stereoselective total synthesis of the natural product. The development of a structural revision hypothesis, its testing, and corroboration are reported. Synthetic (6R,10R,13R,14R,16R,17R,19S,20S,21R,24S,25S,28S,30S,32R, 33R,34R,36S,37S,39R)-Azaspiracid-3 chromatographically and spectroscopically matched naturally occurring Azaspiracid-3, whereas the previously assigned 20R epimer did not.
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total synthesis of 6r 10r 13r 14r 16r 17r 19s 20r 21r 24s 25s 28s 30s 32r 33r 34r 36s 37s 39r Azaspiracid 3 reveals non identity with the natural product
Angewandte Chemie, 2018Co-Authors: Nathaniel T. Kenton, Pearse Mccarron, Zhigao Zhang, Yong Chen, Antony Akura Okumu, Jane Kilcoyne, Daniel Aduampratwum, Son Nguyen, Yue Ding, Frode RiseAbstract:A convergent and stereoselective total synthesis of the previously assigned structure of Azaspiracid-3 has been achieved by a late-stage Nozaki-Hiyama-Kishi coupling to form the C21-C22 bond with the C20 configuration unambiguously established from l-(+)-tartaric acid. Postcoupling steps involved oxidation to an ynone, modified Stryker reduction of the alkyne, global deprotection, and oxidation of the resulting C1 primary alcohol to the carboxylic acid. The synthetic product matched naturally occurring Azaspiracid-3 by mass spectrometry, but differed both chromatographically and spectroscopically.
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Selective Extraction and Purification of Azaspiracids from Blue Mussels (Mytilus edulis) Using Boric Acid Gel
2018Co-Authors: Christopher O Miles, Pearse Mccarron, Ingunn A Samdal, Thomas Rundberget, Jane Kilcoyne, Sabrina D. Giddings, Thor Waaler, Kjersti E. LøvbergAbstract:Azaspiracids belong to a family of more than 50 polyether toxins originating from marine dinoflagellates such as Azadinium spinosum. All of the Azaspiracids reported thus far contain a 21,22-dihydroxy group. Boric acid gel can bind selectively to compounds containing vic-diols or α-hydroxycarboxylic acids via formation of reversible boronate complexes. Here we report use of the gel to selectively capture and release Azaspiracids from extracts of blue mussels. Analysis of the extracts and fractions by liquid chromatography–tandem mass spectrometry (LC–MS) showed that this procedure resulted in an excellent cleanup of the Azaspiracids in the extract. Analysis by enzyme-linked immunoasorbent assay (ELISA) and LC–MS indicated that most Azaspiracid analogues were recovered in good yield by this procedure. The capacity of boric acid gel for Azaspiracids was at least 50 μg/g, making this procedure suitable for use in the early stages of preparative purification of Azaspiracids. In addition to its potential for concentration of dilute samples, the extensive cleanup provided by boric acid gel fractionation of Azaspiracids in mussel samples almost eliminated matrix effects during subsequent LC–MS and could be expected to reduce matrix effects during ELISA analysis. The method may therefore prove useful for quantitative analysis of Azaspiracids as part of monitoring programs. Although LC–MS data showed that okadaic acid analogues also bound to the gel, this was much less efficient than for Azaspiracids under the conditions used. The boric acid gel methodology is potentially applicable to other important groups of natural toxins containing diols including ciguatoxins, palytoxins, pectenotoxins, tetrodotoxin, trichothecenes, and toxin glycosides
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TITLE RUNNING HEAD: Cytotoxicity of natural AZA analogs
2016Co-Authors: Jane Irish, Jane Kilcoyne, Michael J. Twiner, Racha El-ladki, Gregory J. DoucetteAbstract:Comparative effects of the marine algal toxins Azaspiracid-1,-2, and-3 on Jurkat T lymphocyte cell
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Improved Isolation Procedure for Azaspiracids from Shellfish, Structural Elucidation of Azaspiracid-6, and Stability Studies
2016Co-Authors: Jane Kilcoyne, Michael A Quilliam, Philipp Hess, Adela Keogh, Patricia Leblanc, Ger Clancy, Ian Burton, Christopher O MilesAbstract:Azaspiracids are a group of lipophilic polyether toxins produced by the small dinoflagellate Azadinium spinosum. They may accumulate in shellfish and can result in illnesses when consumed by humans. Research into analytical methods, chemistry, metabolism, and toxicology of Azaspiracids has been severely constrained by the scarcity of high-purity Azaspiracids. Consequently, since their discovery in 1995, considerable efforts have been made to develop methods for the isolation of Azaspiracids in sufficient amounts and purities for toxicological studies, in addition to the preparation of standard reference materials. A seven-step procedure was improved for the isolation of Azaspiracids-1–3 (1, 2, and 3) increasing recoveries 2-fold as compared to previous methods and leading to isolation of sufficiently purified Azaspiracid-6 (6) for structural determination by NMR spectroscopy. The procedure, which involved a series of partitioning and column chromatography steps, was performed on 500 g of Mytilus edulis hepatopancreas tissue containing ∼14 mg of 1. Overall yields of 1 (52%), 2 (43%), 3 (43%), and 6 (38%) were good, and purities were confirmed by NMR spectroscopy. The structure of 6 was determined by one- and two-dimensional NMR spectroscopy and mass spectrometry. The stability of 6 relative to 1 was also assessed in three solvents in a short-term study that demonstrated the greatest stability in aqueous acetonitrile
Kevin J James - One of the best experts on this subject based on the ideXlab platform.
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The development of a rapid method for the isolation of four Azaspiracids for use as reference materials for quantitative LC–MS–MS methods
Analytical and Bioanalytical Chemistry, 2010Co-Authors: Isa Ruppen Canás, Brett Hamilton, Kevin J James, Cian Moroney, Keith O’callaghan, Ambrose FureyAbstract:The Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 after consumption of contaminated shellfish ( Mytilus edulis ). Levels of Azaspiracids in shellfish for human consumption are monitored in accordance with EU guidelines: only shellfish with less than 160 μg kg^−1 are deemed safe. The limited availability of commercially available standards for Azaspiracids is a serious problem, because validated LC–MS methods are required for routine analysis of these toxins in shellfish tissues. The procedure described herein has been used for the separation and the isolation of four Azaspiracid (AZA) toxins from shellfish, for use as LC–MS–MS reference materials. Five separation steps have been used to isolate Azaspiracids 1, 2, 3, and 6. The purity of the toxins obtained has been confirmed by multiple mass spectrometric methods using authentic Azaspiracid standards. The same techniques have been used for quantification of the toxins extracted. The isolation procedure involves several chromatographic purification techniques: solid-phase extraction (diol sorbent, 90% mass reduction, and 95 ± 1% toxin recovery); Sephadex size-exclusion chromatography (87% mass reduction and up to 95 ± 2% toxin recovery), Toyopearl HW size-exclusion chromatography (90% mass reduction and up to 92.5 ± 2.5% toxin recovery), and semi-preparative LC (78 ± 3% toxin recovery). The procedure effectively separates the toxins from the sample matrix and furnishes Azaspiracid toxins (AZA1, AZA2, AZA3 and AZA6) of sufficient purity with an average yield of 65% ( n = 5). Triple-quadrupole mass spectrometry was used for qualitative and quantitative monitoring of the isolation efficiency after each stage of the process. High-resolution mass spectrometric evaluation of the toxic isolated material in both positive and negative modes suggests high purity.
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Azaspiracid poisoning azp toxins in shellfish toxicological and health considerations
Toxicon, 2010Co-Authors: Ambrose Furey, Keith Ocallaghan, Mary Lehane, Kevin J James, Sinead OdohertyAbstract:It has been almost a decade since a previously unknown human toxic syndrome, Azaspiracid poisoning (AZP), emerged as the cause of severe gastrointestinal illness in humans after the consumption of mussels (Mytilus edulis). Structural studies indicated that these toxins, Azaspiracids, were of a new unprecedented class containing novel structural features. It is now known that the prevalent Azaspiracids in mussels are AZA1, AZA2 and AZA3, which differ from each other in their degree of methylation. Several hydroxylated and carboxylated analogues of the main Azaspiracids have also been identified, presumed to be metabolites of the main toxins. Since its first discovery in Irish mussels, the development of facile sensitive and selective LC-MS/MS methods has resulted in the discovery of AZA in other countries and in other species. Mice studies indicate that this toxin class can cause serious tissue injury, especially to the small intestine, and chronic exposure may increase the likelihood of the development of lung tumours. Studies also show that tissue recovery is very slow following exposure. These observations suggest that AZA is more dangerous than the other known classes of shellfish toxins. Consequently, in order to protect human consumers, proper risk assessment and regulatory control of shellfish and other affected species is of the utmost importance.
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first evidence of Azaspiracids azas a family of lipophilic polyether marine toxins in scallops argopecten purpuratus and mussels mytilus chilensis collected in two regions of chile
Toxicon, 2010Co-Authors: Americo Lopezrivera, Keith Ocallaghan, Merisa Moriarty, Daniel Odriscoll, Brett Hamilton, Mary Lehane, Kevin J James, Ambrose FureyAbstract:Abstract Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 following the consumption by consumers of intoxicated shellfish (Mytilus edulis). These Azaspiracids have now been identified in mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) from two Chilean locations. This is the first report of the occurrence of Azaspiracid toxins in these species (Mytilus chilensis and Argopecten purpuratus) from Chile. The areas studied were Bahia Inglesa (III Region, 27° SL) and Chiloe Archipelago, both important scallop and mussels farming areas. Separation of Azaspiracid (AZA1), Azaspiracid isomer (AZA6) and its analogues, 8-methylAzaspiracid (AZA2) and 22-demethylAzaspiracid (AZA3), was achieved using reversed-phase LC and toxins were identified using a turbo electrospray ionisation (ESI) source, to a triple quadrupole mass spectrometer. In mussels, AZA1 was the predominant toxin in mussel hepatopancreas with AZA2, AZA3 and AZA6 present in approximate equivalent amounts in the remaining tissues, 20–30% of the AZA1 level. AZA2 predominated in the scallop samples with the toxin almost entirely present in the hepatopancreas (digestive gland). AZA1 was only observed in some of the scallop samples and was present at 12–15% of the AZA2 levels. Whilst the levels of AZAs in Chilean samples are below the EU regulatory limit of 160 μg/kg, it is significant that this toxin is present in Pacific Ocean species. Consequently measures should be taken by regulatory authorities to implement regular seafood monitoring to ensure safety of harvested product.
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Ubiquitous 'benign' alga emerges as the cause of shellfish contamination responsible for the human toxic syndrome, Azaspiracid poisoning.
Toxicon : official journal of the International Society on Toxinology, 2003Co-Authors: Kevin J James, Mary Lehane, Masayuki Satake, Cian Moroney, Takeshi Yasumoto, Cilian Roden, Ambrose FureyAbstract:A new human toxic syndrome, Azaspiracid poisoning (AZP), was identified following illness from the consumption of contaminated mussels (Mytilus edulis). To discover the aetiology of AZP, sensitive analytical protocols involving liquid chromatography-mass spectrometry (LC-MS) were used to screen marine phytoplankton for Azaspiracids. Collections of single species were prepared by manually separating phytoplankton for LC-MS analysis. A dinoflagellate species of the genus, Protoperidinium, has been identified as the progenitor of Azaspiracids. Azaspiracid-1, and its analogues, AZA2 and AZA3, were identified in extracts of 200 cells using electrospray multiple tandem MS. This discovery has significant implications for both human health and the aquaculture industry since this phytoplankton genus was previously considered to be toxicologically benign. The average toxin content was 1.8 fmol of total AZA toxins per cell with AZA1 as the predominant toxin, accounting for 82% of the total.
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first evidence of an extensive northern european distribution of Azaspiracid poisoning azp toxins in shellfish
Toxicon, 2002Co-Authors: Kevin J James, Mary Lehane, Ambrose Furey, Masayuki Satake, Hanne Ramstad, Tore Aune, Peter Hovgaard, Steven Morris, Wendy Higman, Takeshi YasumotoAbstract:Azaspiracids have recently been identified as the toxins responsible for a series of human intoxications in Europe since 1995, following the consumption of cultured mussels (Mytilus edulis) from the west coast of Ireland. Liquid chromatography–mass spectrometric (LC–MS) methods have been applied in the study reported here to investigate the new human toxic syndrome, Azaspiracid poisoning. Separation of Azaspiracid (AZA1) and its analogues, 8-methylAzaspiracid (AZA2) and 22-demethylAzaspiracid (AZA3), was achieved using reversed-phase LC and coupled, via an electrospray ionisation source, to an ion-trap mass spectrometer. These Azaspiracids have now been identified in mussels from Craster (north-east England) and Sognefjord (south-west Norway) using source collision induced dissociation-MS and multiple tandem MS detection. AZA1 was the predominant toxin and toxin profiles were similar to those found in contaminated Irish shellfish. This is the first report of the occurrence of these Azaspiracids outside Ireland with the significant implications that these toxins may occur in shellfish throughout northern Europe.
Ambrose Furey - One of the best experts on this subject based on the ideXlab platform.
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The development of a rapid method for the isolation of four Azaspiracids for use as reference materials for quantitative LC–MS–MS methods
Analytical and Bioanalytical Chemistry, 2010Co-Authors: Isa Ruppen Canás, Brett Hamilton, Kevin J James, Cian Moroney, Keith O’callaghan, Ambrose FureyAbstract:The Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 after consumption of contaminated shellfish ( Mytilus edulis ). Levels of Azaspiracids in shellfish for human consumption are monitored in accordance with EU guidelines: only shellfish with less than 160 μg kg^−1 are deemed safe. The limited availability of commercially available standards for Azaspiracids is a serious problem, because validated LC–MS methods are required for routine analysis of these toxins in shellfish tissues. The procedure described herein has been used for the separation and the isolation of four Azaspiracid (AZA) toxins from shellfish, for use as LC–MS–MS reference materials. Five separation steps have been used to isolate Azaspiracids 1, 2, 3, and 6. The purity of the toxins obtained has been confirmed by multiple mass spectrometric methods using authentic Azaspiracid standards. The same techniques have been used for quantification of the toxins extracted. The isolation procedure involves several chromatographic purification techniques: solid-phase extraction (diol sorbent, 90% mass reduction, and 95 ± 1% toxin recovery); Sephadex size-exclusion chromatography (87% mass reduction and up to 95 ± 2% toxin recovery), Toyopearl HW size-exclusion chromatography (90% mass reduction and up to 92.5 ± 2.5% toxin recovery), and semi-preparative LC (78 ± 3% toxin recovery). The procedure effectively separates the toxins from the sample matrix and furnishes Azaspiracid toxins (AZA1, AZA2, AZA3 and AZA6) of sufficient purity with an average yield of 65% ( n = 5). Triple-quadrupole mass spectrometry was used for qualitative and quantitative monitoring of the isolation efficiency after each stage of the process. High-resolution mass spectrometric evaluation of the toxic isolated material in both positive and negative modes suggests high purity.
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Azaspiracid poisoning azp toxins in shellfish toxicological and health considerations
Toxicon, 2010Co-Authors: Ambrose Furey, Keith Ocallaghan, Mary Lehane, Kevin J James, Sinead OdohertyAbstract:It has been almost a decade since a previously unknown human toxic syndrome, Azaspiracid poisoning (AZP), emerged as the cause of severe gastrointestinal illness in humans after the consumption of mussels (Mytilus edulis). Structural studies indicated that these toxins, Azaspiracids, were of a new unprecedented class containing novel structural features. It is now known that the prevalent Azaspiracids in mussels are AZA1, AZA2 and AZA3, which differ from each other in their degree of methylation. Several hydroxylated and carboxylated analogues of the main Azaspiracids have also been identified, presumed to be metabolites of the main toxins. Since its first discovery in Irish mussels, the development of facile sensitive and selective LC-MS/MS methods has resulted in the discovery of AZA in other countries and in other species. Mice studies indicate that this toxin class can cause serious tissue injury, especially to the small intestine, and chronic exposure may increase the likelihood of the development of lung tumours. Studies also show that tissue recovery is very slow following exposure. These observations suggest that AZA is more dangerous than the other known classes of shellfish toxins. Consequently, in order to protect human consumers, proper risk assessment and regulatory control of shellfish and other affected species is of the utmost importance.
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first evidence of Azaspiracids azas a family of lipophilic polyether marine toxins in scallops argopecten purpuratus and mussels mytilus chilensis collected in two regions of chile
Toxicon, 2010Co-Authors: Americo Lopezrivera, Keith Ocallaghan, Merisa Moriarty, Daniel Odriscoll, Brett Hamilton, Mary Lehane, Kevin J James, Ambrose FureyAbstract:Abstract Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 following the consumption by consumers of intoxicated shellfish (Mytilus edulis). These Azaspiracids have now been identified in mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) from two Chilean locations. This is the first report of the occurrence of Azaspiracid toxins in these species (Mytilus chilensis and Argopecten purpuratus) from Chile. The areas studied were Bahia Inglesa (III Region, 27° SL) and Chiloe Archipelago, both important scallop and mussels farming areas. Separation of Azaspiracid (AZA1), Azaspiracid isomer (AZA6) and its analogues, 8-methylAzaspiracid (AZA2) and 22-demethylAzaspiracid (AZA3), was achieved using reversed-phase LC and toxins were identified using a turbo electrospray ionisation (ESI) source, to a triple quadrupole mass spectrometer. In mussels, AZA1 was the predominant toxin in mussel hepatopancreas with AZA2, AZA3 and AZA6 present in approximate equivalent amounts in the remaining tissues, 20–30% of the AZA1 level. AZA2 predominated in the scallop samples with the toxin almost entirely present in the hepatopancreas (digestive gland). AZA1 was only observed in some of the scallop samples and was present at 12–15% of the AZA2 levels. Whilst the levels of AZAs in Chilean samples are below the EU regulatory limit of 160 μg/kg, it is significant that this toxin is present in Pacific Ocean species. Consequently measures should be taken by regulatory authorities to implement regular seafood monitoring to ensure safety of harvested product.
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Ubiquitous 'benign' alga emerges as the cause of shellfish contamination responsible for the human toxic syndrome, Azaspiracid poisoning.
Toxicon : official journal of the International Society on Toxinology, 2003Co-Authors: Kevin J James, Mary Lehane, Masayuki Satake, Cian Moroney, Takeshi Yasumoto, Cilian Roden, Ambrose FureyAbstract:A new human toxic syndrome, Azaspiracid poisoning (AZP), was identified following illness from the consumption of contaminated mussels (Mytilus edulis). To discover the aetiology of AZP, sensitive analytical protocols involving liquid chromatography-mass spectrometry (LC-MS) were used to screen marine phytoplankton for Azaspiracids. Collections of single species were prepared by manually separating phytoplankton for LC-MS analysis. A dinoflagellate species of the genus, Protoperidinium, has been identified as the progenitor of Azaspiracids. Azaspiracid-1, and its analogues, AZA2 and AZA3, were identified in extracts of 200 cells using electrospray multiple tandem MS. This discovery has significant implications for both human health and the aquaculture industry since this phytoplankton genus was previously considered to be toxicologically benign. The average toxin content was 1.8 fmol of total AZA toxins per cell with AZA1 as the predominant toxin, accounting for 82% of the total.
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first evidence of an extensive northern european distribution of Azaspiracid poisoning azp toxins in shellfish
Toxicon, 2002Co-Authors: Kevin J James, Mary Lehane, Ambrose Furey, Masayuki Satake, Hanne Ramstad, Tore Aune, Peter Hovgaard, Steven Morris, Wendy Higman, Takeshi YasumotoAbstract:Azaspiracids have recently been identified as the toxins responsible for a series of human intoxications in Europe since 1995, following the consumption of cultured mussels (Mytilus edulis) from the west coast of Ireland. Liquid chromatography–mass spectrometric (LC–MS) methods have been applied in the study reported here to investigate the new human toxic syndrome, Azaspiracid poisoning. Separation of Azaspiracid (AZA1) and its analogues, 8-methylAzaspiracid (AZA2) and 22-demethylAzaspiracid (AZA3), was achieved using reversed-phase LC and coupled, via an electrospray ionisation source, to an ion-trap mass spectrometer. These Azaspiracids have now been identified in mussels from Craster (north-east England) and Sognefjord (south-west Norway) using source collision induced dissociation-MS and multiple tandem MS detection. AZA1 was the predominant toxin and toxin profiles were similar to those found in contaminated Irish shellfish. This is the first report of the occurrence of these Azaspiracids outside Ireland with the significant implications that these toxins may occur in shellfish throughout northern Europe.
