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Testing metal\u2010based anticancer compounds with high\u2010throughput zebrafish toxicological assays requires analytical methods with the sensitivity to detect these sublethal tissue doses in very small sample masses (e.g., egg mass 100\u00a0\u03bcg). A robust bioanalytical model, zebrafish embryos coupled with inductively coupled plasma\u2010mass spectrometry (ICPMS) for measurement of delivered dose, creates a very effective means for screening metal\u2010based chemotherapeutic agents. In this study, we used ICPMS quantitation with the zebrafish embryo assays to detect metal equivalents at multiple response endpoints for two compounds, the chemotherapeutic agent cisplatin and ruthenium (Ru)\u2010based prospective metallodrug, PMC79. We hypothesized that cisplatin and PMC79 have different mechanisms for inducing apoptosis and result in similar lesions but different potencies following water\u2010borne exposure. An ICPMS method was developed to detect the metal in waterborne solution and tissue (detection limit: 5 parts per trillion for Ru or platinum [Pt]). The Ru\u2010based compound was more potent (LC<jats:sub>50<\/jats:sub>: 7.8\u00a0\u03bc<jats:sc>m<\/jats:sc>) than cisplatin (LC<jats:sub>50<\/jats:sub>: 158\u00a0\u03bc<jats:sc>m<\/jats:sc>) and induced disparate lesions. Lethality from cisplatin exposure exhibited a threshold (values &gt;15\u00a0mg\/L) while no threshold was observed for delayed hatching (lowest observed adverse effect level 3.75\u00a0mg\/L cisplatin; 8.7 Pt (ng)\/organism). The Ru organometallic did not have a threshold for lethality. Cisplatin\u2010induced delayed hatching was investigated further by larval\u2010Pt distribution and preferentially distributed to the chorion. We propose that zebrafish embryo\u2010larval assays coupled with ICPMS serve as a powerful platform to evaluate relative potency and toxic effects of metallodrug candidates.<\/jats:p>","DOI":"10.1002\/jat.3802","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T21:25:20Z","timestamp":1554758720000},"page":"1173-1180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A novel screening method for transition metal\u2010based anticancer compounds using zebrafish embryo\u2010larval assay and inductively coupled plasma\u2010mass spectrometry analysis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1738-7235","authenticated-orcid":false,"given":"Brittany F.","family":"Karas","sequence":"first","affiliation":[{"name":"Joint Graduate Program in Toxicology Rutgers, The State University of New Jersey  Piscataway NJ 08854 USA"},{"name":"Environmental and Occupational Health Sciences Institute Rutgers University  170 Frelinghuysen Road Piscataway NJ 08854 USA"},{"name":"Department of Biochemistry and Microbiology Rutgers University  76 Lipman Drive New Brunswick NJ 08854 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonor","family":"C\u00f4rte\u2010Real","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias da Universidade de Lisboa  Campo Grande 1749\u2010016 Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-6330","authenticated-orcid":false,"given":"Cathleen L.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute Rutgers University  170 Frelinghuysen Road Piscataway NJ 08854 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia","family":"Valente","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias da Universidade de Lisboa  Campo Grande 1749\u2010016 Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-5270","authenticated-orcid":false,"given":"Keith R.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute Rutgers University  170 Frelinghuysen Road Piscataway NJ 08854 USA"},{"name":"Department of Biochemistry and Microbiology Rutgers University  76 Lipman Drive New Brunswick NJ 08854 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-4321","authenticated-orcid":false,"given":"Brian T.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute Rutgers University  170 Frelinghuysen Road Piscataway NJ 08854 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.12.022"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.08.112"},{"key":"e_1_2_7_4_1","unstructured":"Fresenius Kabi USA LLC(2017).Cisplatin\u2014cisplatin injection solution [package insert]. 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