{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:39:21Z","timestamp":1780468761169,"version":"3.54.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A simple, sensitive and high throughput LC-MS\/MS method was developed and validated for quantification of fipronil, fipronil sulfone and fipronil desulfinyl in rat and human dried blood spots (DBS). DBS samples were prepared by spiking 10\u2009\u03bcl blood on DMPK-C cards followed by drying at room temperature. The whole blood spots were then punched from the card and extracted using acetonitrile. The total chromatographic run time of the method was only 2\u2009min. The lower limit of quantification of the method was 0.1\u2009ng\/ml for all the analytes. The method was successfully applied to determine fipronil desulfinyl in DBS samples obtained from its toxicokinetic study in rats following intravenous dose (1\u2009mg\/kg). In conclusion, the proposed DBS methodology has significant potential in toxicokinetics and biomonitoring studies of environmental toxicants. This microvolume DBS technique will be an ideal tool for biomonitoring studies, particularly in paediatric population. Small volume requirements, minimally invasive blood sampling method, easier storage and shipping procedure make DBS a suitable technique for such studies. Further, DBS technique contributes towards the principles of 3Rs resulting in significant reduction in the number of rodents used and refinement in sample collection for toxicokinetic studies.<\/jats:p>","DOI":"10.1038\/srep22447","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T10:02:20Z","timestamp":1457604140000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["DBS-platform for biomonitoring and toxicokinetics of toxicants: proof of concept using LC-MS\/MS analysis of fipronil and its metabolites in blood"],"prefix":"10.1038","volume":"6","author":[{"given":"Kanumuri Siva Rama","family":"Raju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Taneja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamunur","family":"Rashid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish Kumar","family":"Sonkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Wahajuddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheelendra Pratap","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,10]]},"reference":[{"key":"BFsrep22447_CR1","unstructured":"Brassard, D., Haddad, S. & Hill, E. US EPA BEAD Chemical Profile for Registration Review: Fipronil (PC Code: 129121). (2011)."},{"key":"BFsrep22447_CR2","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1584\/jpestics.R07-02","volume":"32","author":"AS Gunasekara","year":"2007","unstructured":"Gunasekara, A. S., Truong, T., Goh, K. S., Spurlock, F. & Tjeerdema, R. S. Environmental fate and toxicology of fipronil. J. Pesticide Sci. 32, 189\u2013199 (2007).","journal-title":"J. Pesticide Sci."},{"key":"BFsrep22447_CR3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/ps.830","volume":"60","author":"T Ikeda","year":"2004","unstructured":"Ikeda, T., Nagata, K., Kono, Y., Yeh, J. Z. & Narahashi, T. Fipronil modulation of GABAA receptor single-channel currents. Pest Manag. Sci. 60, 487\u2013492, 10.1002\/ps.830 (2004).","journal-title":"Pest Manag. Sci."},{"key":"BFsrep22447_CR4","first-page":"1","volume":"176","author":"CC Tingle","year":"2003","unstructured":"Tingle, C. C., Rother, J. A., Dewhurst, C. F., Lauer, S. & King, W. J. Fipronil: environmental fate, ecotoxicology, and human health concerns. Rev. Environ. Contam. Toxicol. 176, 1\u201366 (2003).","journal-title":"Rev. Environ. Contam. Toxicol."},{"key":"BFsrep22447_CR5","doi-asserted-by":"publisher","first-page":"12764","DOI":"10.1073\/pnas.93.23.12764","volume":"93","author":"D Hainzl","year":"1996","unstructured":"Hainzl, D. & Casida, J. E. Fipronil insecticide: Novel photochemical desulfinylation with retention of neurotoxicity. P. Natl. Acad. Sci. USA 93, 12764\u201312767, 10.1073\/pnas.93.23.12764 (1996).","journal-title":"P. Natl. Acad. Sci. USA"},{"key":"BFsrep22447_CR6","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1021\/tx980157t","volume":"11","author":"D Hainzl","year":"1998","unstructured":"Hainzl, D., Cole, L. M. & Casida, J. E. Mechanisms for selective toxicity of fipronil insecticide and its sulfone metabolite and desulfinyl photoproduct. Chem. Res. Toxicol. 11, 1529\u20131535, 10.1021\/tx980157t (1998).","journal-title":"Chem. Res. Toxicol."},{"key":"BFsrep22447_CR7","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1016\/j.chemosphere.2013.07.083","volume":"93","author":"JP Cravedi","year":"2013","unstructured":"Cravedi, J. P., Delous, G., Zalko, D., Viguie, C. & Debrauwer, L. Disposition of fipronil in rats. Chemosphere 93, 2276\u20132283, 10.1016\/j.chemosphere.2013.07.083 (2013).","journal-title":"Chemosphere"},{"key":"BFsrep22447_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.envint.2015.01.016","volume":"78","author":"RL McMahen","year":"2015","unstructured":"McMahen, R. L. et al. Identification of fipronil metabolites by time-of-flight mass spectrometry for application in a human exposure study. Environ. Int. 78, 16\u201323, 10.1016\/j.envint.2015.01.016 (2015).","journal-title":"Environ. Int."},{"key":"BFsrep22447_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.cbi.2004.03.002","volume":"147","author":"J Tang","year":"2004","unstructured":"Tang, J., Amin Usmani, K., Hodgson, E. & Rose, R. L. In vitro metabolism of fipronil by human and rat cytochrome P450 and its interactions with testosterone and diazepam. Chem. Biol. Interact. 147, 319\u2013329, 10.1016\/j.cbi.2004.03.002 (2004).","journal-title":"Chem. Biol. Interact."},{"key":"BFsrep22447_CR10","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.cbi.2006.09.013","volume":"164","author":"PC Das","year":"2006","unstructured":"Das, P. C., Cao, Y., Cherrington, N., Hodgson, E. & Rose, R. L. Fipronil induces CYP isoforms and cytotoxicity in human hepatocytes. Chem. Biol. Iinteract. 164, 200\u2013214, 10.1016\/j.cbi.2006.09.013 (2006).","journal-title":"Chem. Biol. Iinteract."},{"key":"BFsrep22447_CR11","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1089\/thy.2010.0449","volume":"21","author":"F Herin","year":"2011","unstructured":"Herin, F. et al. Thyroid function tests in persons with occupational exposure to fipronil. Thyroid 21, 701\u2013706, 10.1089\/thy.2010.0449 (2011).","journal-title":"Thyroid"},{"key":"BFsrep22447_CR12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.tox.2008.09.026","volume":"255","author":"J Leghait","year":"2009","unstructured":"Leghait, J. et al. Fipronil-induced disruption of thyroid function in rats is mediated by increased total and free thyroxine clearances concomitantly to increased activity of hepatic enzymes. Toxicology 255, 38\u201344, 10.1016\/j.tox.2008.09.026 (2009).","journal-title":"Toxicology"},{"key":"BFsrep22447_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/toxsci\/kfs094","volume":"127","author":"BB Roques","year":"2012","unstructured":"Roques, B. B. et al. CYP450-dependent biotransformation of the insecticide fipronil into fipronil sulfone can mediate fipronil-induced thyroid disruption in rats. Toxicol. Sci. 127, 29\u201341, 10.1093\/toxsci\/kfs094 (2012).","journal-title":"Toxicol. Sci."},{"key":"BFsrep22447_CR14","doi-asserted-by":"publisher","first-page":"737","DOI":"10.3109\/15563650.2010.507548","volume":"48","author":"SJ Lee","year":"2010","unstructured":"Lee, S. J. et al. Acute illnesses associated with exposure to fipronil--surveillance data from 11 states in the United States, 2001-2007. Clin. Toxicol. 48, 737\u2013744, 10.3109\/15563650.2010.507548 (2010).","journal-title":"Clin. Toxicol."},{"key":"BFsrep22447_CR15","first-page":"955","volume":"42","author":"F Mohamed","year":"2004","unstructured":"Mohamed, F. et al. Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil\u2013a GABAA-gated chloride channel blocker. J. Toxicol. 42, 955\u2013963 (2004).","journal-title":"J. Toxicol."},{"key":"BFsrep22447_CR16","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.pestbp.2010.12.007","volume":"99","author":"PRG Ter\u00e7ariol","year":"2011","unstructured":"Ter\u00e7ariol, P. R. G. & Godinho, A. F. Behavioral effects of acute exposure to the insecticide fipronil. Pesticide. Biochem. Physiol. 99, 221\u2013225 (2011).","journal-title":"Pesticide. Biochem. Physiol."},{"key":"BFsrep22447_CR17","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1021\/es202904x","volume":"46","author":"J Gan","year":"2012","unstructured":"Gan, J., Bondarenko, S., Oki, L., Haver, D. & Li, J. X. Occurrence of fipronil and its biologically active derivatives in urban residential runoff. Environ. Sci. Tech. 46, 1489\u20131495, 10.1021\/es202904x (2012).","journal-title":"Environ. Sci. Tech."},{"key":"BFsrep22447_CR18","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1016\/j.jchromb.2010.05.018","volume":"878","author":"MZ Lacroix","year":"2010","unstructured":"Lacroix, M. Z., Puel, S., Toutain, P. L. & Viguie, C. Quantification of fipronil and its metabolite fipronil sulfone in rat plasma over a wide range of concentrations by LC\/UV\/MS. J. Chromatogr. B 878, 1934\u20131938, 10.1016\/j.jchromb.2010.05.018 (2010).","journal-title":"J. Chromatogr. B"},{"key":"BFsrep22447_CR19","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1093\/jat\/28.8.660","volume":"28","author":"A Ramesh","year":"2004","unstructured":"Ramesh, A. & Ravi, P. E. Negative ion chemical ionization-gas chromatographic-mass spectrometric determination of residues of different pyrethroid insecticides in whole blood and serum. J. Anal. Toxicol. 28, 660\u2013666 (2004).","journal-title":"J. Anal. Toxicol."},{"key":"BFsrep22447_CR20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/bmc.1367","volume":"24","author":"W Li","year":"2010","unstructured":"Li, W. & Tse, F. L. Dried blood spot sampling in combination with LC-MS\/MS for quantitative analysis of small molecules. Biomed. Chromatogr. 24, 49\u201365, 10.1002\/bmc.1367 (2010).","journal-title":"Biomed. Chromatogr."},{"key":"BFsrep22447_CR21","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.4155\/bio.13.180","volume":"5","author":"I Taneja","year":"2013","unstructured":"Taneja, I., Erukala, M., Raju, K. S. & Singh, S. P. & Wahajuddin. Dried blood spots in bioanalysis of antimalarials: relevance and challenges in quantitative assessment of antimalarial drugs. Bioanalysis 5, 2171\u20132186, 10.4155\/bio.13.180 (2013).","journal-title":"Bioanalysis"},{"key":"BFsrep22447_CR22","unstructured":"USFDA. Guidance for industry: bioanalytical method validation. Guidance for Industry: Bioanalytical Method Validation, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Rockville, MD, USA (2013)."},{"key":"BFsrep22447_CR23","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1002\/rcm.4990","volume":"25","author":"G Liu","year":"2011","unstructured":"Liu, G., Snapp, H. M. & Ji, Q. C. Internal standard tracked dilution to overcome challenges in dried blood spots and robotic sample preparation for liquid chromatography\/tandem mass spectrometry assays. Rapid Comm. Mass Spectrom. 25, 1250\u20131256, 10.1002\/rcm.4990 (2011).","journal-title":"Rapid Comm. Mass Spectrom."},{"key":"BFsrep22447_CR24","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1023\/A:1018943613122","volume":"10","author":"B Davies","year":"1993","unstructured":"Davies, B. & Morris, T. Physiological parameters in laboratory animals and humans. Pharmaceut. Res. 10, 1093\u20131095 (1993).","journal-title":"Pharmaceut. Res."},{"key":"BFsrep22447_CR25","doi-asserted-by":"publisher","first-page":"967","DOI":"10.4155\/bio.14.253","volume":"7","author":"KS Rama Raju","year":"2015","unstructured":"Rama Raju, K. S. et al. Simultaneous determination of centchroman and tamoxifen along with their metabolites in rat plasma using LC-MS\/MS. Bioanalysis 7, 967\u2013979, 10.4155\/bio.14.253 (2015).","journal-title":"Bioanalysis"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep22447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22447","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep22447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:55:13Z","timestamp":1672890913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep22447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,10]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,3,21]]}},"alternative-id":["BFsrep22447"],"URL":"https:\/\/doi.org\/10.1038\/srep22447","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,10]]},"assertion":[{"value":"13 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22447"}}