{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:42:36Z","timestamp":1760985756963,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T00:00:00Z","timestamp":1544745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch ministry of Agriculture, Nature and Food Quality","award":["KB-23-002-21"],"award-info":[{"award-number":["KB-23-002-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Palytoxin (PlTX) and analogues are produced by certain dinoflagellates, sea anemones, corals and cyanobacteria. PlTX can accumulate in the food chain and when consumed it may cause intoxication with symptoms like myalgia, weakness, fever, nausea, and vomiting. The analysis of PlTXs is challenging, and because of the large molecular structure, it is difficult to develop a sensitive and selective liquid chromatography-mass spectrometry (LC-MS\/MS) method. In this work, an LC-MS\/MS method was developed to analyse PlTXs with use of lithium iodine and formic acid as additives in the mobile phase. For method development, initially, LC-hrMS was used to accurately determine the elemental composition of the precursor and product ions. The main adduct formed was [M + H + 2Li]3+. Fragments were identified with LC-hrMS and these were incorporated in the LC-MS\/MS method. A method of 10 min was developed and a solid phase extraction clean-up procedure was optimised for shellfish matrix. The determined limits of detection were respectively 8 and 22 \u00b5g PlTX kg\u22121 for mussel and oyster matrix. Oysters gave a low recovery of approximately 50% for PlTX during extraction. The method was successfully in-house validated, repeatability had a relative standard deviation less than 20% (n = 5) at 30 \u00b5g PlTX kg\u22121 in mussel, cockle, and ensis, and at 60 \u00b5g PlTX kg\u22121 in oyster.<\/jats:p>","DOI":"10.3390\/toxins10120537","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T12:11:08Z","timestamp":1544789468000},"page":"537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Sensitive LC-MS\/MS Method for Palytoxin Using Lithium Cationization"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1072-7177","authenticated-orcid":false,"given":"Mirjam D.","family":"Klijnstra","sequence":"first","affiliation":[{"name":"RIKILT, Wageningen University and Research Center, Akkermaalsbos 2, 6708 WB Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-1516","authenticated-orcid":false,"given":"Arjen","family":"Gerssen","sequence":"additional","affiliation":[{"name":"RIKILT, Wageningen University and Research Center, Akkermaalsbos 2, 6708 WB Wageningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1021\/ja00124a034","article-title":"Palytoxin analogs from the dinoflagellate ostreopsis siamensis","volume":"117","author":"Usami","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1021\/ja210784u","article-title":"Isolation and structure elucidation of ovatoxin-a, the major toxin produced by ostreopsis ovata","volume":"134","author":"Ciminiello","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/00288330.2002.9517118","article-title":"Uptake of palytoxin-like compounds by shellfish fed ostreopsis siamensis (dinophyceae)","volume":"36","author":"Rhodes","year":"2002","journal-title":"N. Z. J. Mar. Freshw. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/j.1529-8817.2004.04016.x","article-title":"First evidence of palytoxin analogues from an ostreopsis mascarenensis (dinophyceae) benthic bloom in southwestern indian ocean1","volume":"40","author":"Lenoir","year":"2004","journal-title":"J. Phycol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7438","DOI":"10.1021\/acs.analchem.7b01003","article-title":"First identification of palytoxin-like molecules in the atlantic coral species palythoa canariensis","volume":"89","author":"Fraga","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kerbrat, A.S., Amzil, Z., Pawlowiez, R., Golubic, S., Sibat, M., Darius, H.T., Chinain, M., and Laurent, D. (2011). First evidence of palytoxin and 42-hydroxy-palytoxin in the marine cyanobacterium trichodesmium. Mar. Drugs, 9.","DOI":"10.3390\/md9040543"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.toxicon.2010.05.010","article-title":"World-wide occurrence of the toxic dinoflagellate genus ostreopsis schmidt","volume":"57","author":"Rhodes","year":"2011","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.toxicon.2010.11.014","article-title":"Occurrence of palytoxin-group toxins in seafood and future strategies to complement the present state of the art","volume":"57","author":"Aligizaki","year":"2011","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ciminiello, P., Dell\u2019Aversano, C., and Forino, M. (2015). Chemistry of palytoxin and its analogues. Phycotoxins: Chemistry and Biochemistry, Wiley-Blackwell. [2nd ed.].","DOI":"10.1002\/9781118500354.ch5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13920","DOI":"10.1021\/acs.est.7b03827","article-title":"Variability in toxin profiles of the mediterranean ostreopsis cf. Ovata and in structural features of the produced ovatoxins","volume":"51","author":"Tartaglione","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.toxicon.2009.05.035","article-title":"Human risk associated with palytoxin exposure","volume":"56","author":"Deeds","year":"2010","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.etap.2017.08.010","article-title":"Prevalence and characteristics of inhalational and dermal palytoxin exposures reported to the national poison data system in the U.S","volume":"55","author":"Murphy","year":"2017","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_13","first-page":"3212","article-title":"Ostreopsis ovata and human health: Epidemiological and clinical features of respiratory syndrome outbreaks from a two-year syndromic surveillance, 2005\u201306, in North-West Italy","volume":"12","author":"Durando","year":"2007","journal-title":"Wkly. Releases (1997\u20132007)"},{"key":"ref_14","first-page":"A4200","article-title":"Family with fever after cleaning a sea aquarium","volume":"156","author":"Snoeks","year":"2012","journal-title":"Ned. Tijdschr. Geneeskd."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00204-017-2105-8","article-title":"Palytoxin congeners","volume":"92","author":"Patocka","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0014-2999(03)01459-6","article-title":"Palytoxin-induced increase in cytosolic-free Ca2+ in mouse spleen cells","volume":"465","author":"Satoh","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/0041-0101(74)90011-7","article-title":"Toxicological evaluation of palytoxin in several animal species","volume":"12","author":"Wiles","year":"1974","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.toxlet.2009.09.009","article-title":"Palytoxin toxicity after acute oral administration in mice","volume":"191","author":"Sosa","year":"2009","journal-title":"Toxicol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"EFSA (2009). Scientific opinion on marine biotoxins in shellfish\u2013palytoxin group. EFSA J., 1393, 1\u201340.","DOI":"10.2903\/j.efsa.2009.1393"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.toxicon.2010.09.012","article-title":"Palytoxins: Biological and chemical determination","volume":"57","author":"Franco","year":"2011","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ab.2012.02.014","article-title":"Palytoxin detection and quantification using the fluorescence polarization technique","volume":"424","author":"Alfonso","year":"2012","journal-title":"Anal. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.tiv.2015.10.001","article-title":"Exploration of new functional endpoints in neuro-2a cells for the detection of the marine biotoxins saxitoxin, palytoxin and tetrodotoxin","volume":"30","author":"Nicolas","year":"2015","journal-title":"Toxicol. in Vitro"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.toxicon.2016.06.013","article-title":"A revisited hemolytic assay for palytoxin detection: Limitations for its quantitation in mussels","volume":"119","author":"Brovedani","year":"2016","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aca.2015.09.040","article-title":"Detection of palytoxin-like compounds by a flow cytometry-based immunoassay supported by functional and analytical methods","volume":"903","author":"Fraga","year":"2016","journal-title":"Ana. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1007\/s00216-014-8367-6","article-title":"Liquid chromatography\u2013high-resolution mass spectrometry for palytoxins in mussels","volume":"407","author":"Ciminiello","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s00216-014-8338-y","article-title":"The novel ovatoxin-g and isobaric palytoxin (so far referred to as putative palytoxin) from ostreopsis cf. Ovata (nw mediterranean sea): Structural insights by lc-high resolution msn","volume":"407","author":"Tartaglione","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.toxicon.2012.05.024","article-title":"A sensitive assay for palytoxins, ovatoxins and ostreocins using lc-ms\/ms analysis of cleavage fragments from micro-scale oxidation","volume":"60","author":"Selwood","year":"2012","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1021\/acs.est.5b04749","article-title":"Ovatoxin-a, a palytoxin analogue isolated from ostreopsis cf. Ovata fukuyo: Cytotoxic activity and elisa detection","volume":"50","author":"Pelin","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1044-0305(97)00124-4","article-title":"Tandem mass spectrometry of alkali cationized polysaccharides in a quadrupole ion trap","volume":"8","author":"Asam","year":"1997","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s11746-015-2604-9","article-title":"Quantitative analysis of tag in oils using lithium cationization and direct-infusion esi tandem mass spectrometry","volume":"92","author":"Ramaley","year":"2015","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s13361-014-1009-6","article-title":"The competitive influence of Li+, Na+, K+, Ag+, and H+ on the fragmentation of a pegylated polymeric excipient","volume":"26","author":"Wei","year":"2015","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1021\/ac061743r","article-title":"Oxidation artifacts in the electrospray mass spectrometry of a\u03b2 peptide","volume":"79","author":"Chen","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.toxicon.2011.11.013","article-title":"Investigations into matrix components affecting the performance of the official bioassay reference method for quantitation of paralytic shellfish poisoning toxins in oysters","volume":"59","author":"Turner","year":"2012","journal-title":"Toxicon"},{"key":"ref_34","unstructured":"EU Reference Laboratories for Residues of Pesticides (2018, December 14). Sante\/11945\/2015-Guidance Document on Analytical Quality Control and Method Validation Procedures for Pesticides Residues Analysis in Food and Feed. Available online: https:\/\/www.accredia.it\/en\/documento\/guidance-sante-119452015-guidance-document-on-analytical-quality-control-and-method-validation-procedures-for-pesticides-residues-analysis-in-food-and-feed\/."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/jms.4281","article-title":"Design of experiments for the optimization of electrospray ionization in the lc-ms\/ms analysis of ciguatoxins","volume":"53","author":"Moreiras","year":"2018","journal-title":"J. Mass Spectrom."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/12\/537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:33:58Z","timestamp":1760196838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/12\/537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,14]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["toxins10120537"],"URL":"https:\/\/doi.org\/10.3390\/toxins10120537","relation":{},"ISSN":["2072-6651"],"issn-type":[{"type":"electronic","value":"2072-6651"}],"subject":[],"published":{"date-parts":[[2018,12,14]]}}}