{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:26:29Z","timestamp":1790702789191,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016875","name":"Chimerix","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011072","name":"Center for AIDS Research, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["P30 AI050410"],"award-info":[{"award-number":["P30 AI050410"]}],"id":[{"id":"10.13039\/100011072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Brincidofovir (BCV) is an investigational lipid conjugate of the nucleotide analog cidofovir (CDV), which is being developed as a medical countermeasure for the treatment of smallpox. BCV is active against double\u2010stranded DNA viruses including BK and JC viruses. Here, we validated procedures for quantifying BCV and its pharmacologically active moiety cidofovir diphosphate (CDV\u2010PP) in mouse kidney, brain and spleen tissue homogenates. Following homogenization, BCV and CDV\u2010PP were extracted from the tissues by protein precipitation with their stable, isotopically labeled internal standards, BCV\u2010d<jats:sub>6<\/jats:sub> and <jats:sup>13<\/jats:sup>C<jats:sub>3<\/jats:sub><jats:sup>15<\/jats:sup>N<jats:sub>2<\/jats:sub>\u2010CDV\u2010PP. Then, samples were analyzed for BCV by reverse\u2010phase chromatography on a Waters Xterra MS C<jats:sub>18<\/jats:sub> (50\u2009\u00d7\u20092.1\u2009mm, 3.5\u2009\u03bcm particle size) column while CDV\u2010PP was analyzed on a Thermo BioBasic AX (50\u2009\u00d7\u20092.1\u2009mm, 5\u2009\u03bcm particle size) column using anion exchange chromatography. Detection was achieved by electrospray ionization in positive ion mode on an AB Sciex API\u20105000 triple quadrupole mass spectrometer. The calibration curves were linear over a range of 1.00\u20131,000\u2009ng\/ml homogenate and 0.050\u201350.0\u2009ng\/ml homogenate for BCV and CDV\u2010PP, respectively. These methods were validated according to US Food and Drug Administration guidance for industry and may be used to characterize the tissue pharmacology of both analytes to advance its preclinical development.<\/jats:p>","DOI":"10.1002\/bmc.5061","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T02:09:26Z","timestamp":1609812566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A quantitative LC\u2013MS\/MS method for the determination of tissue brincidofovir and cidofovir diphosphate in a MuPyV\u2010infected mouse model"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2711-9533","authenticated-orcid":false,"given":"Bryan B.","family":"Guzman","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7026-7224","authenticated-orcid":false,"given":"Amanda P.","family":"Schauer","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Chimerix, Inc.  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0291-5111","authenticated-orcid":false,"given":"Mackenzie L.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Sykes","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina at Chapel Hill  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.01.008"},{"key":"e_1_2_6_3_1","unstructured":"FDA. (2015).Analytical procedures and methods validation for drugs and biologics. 80 FR 44357."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw172.1886"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2017.04.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020439"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/v2122740"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2005.11.009"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00138"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007365"},{"key":"e_1_2_6_11_1","unstructured":"Naderer O Pharm D. Colton H. Jin G. Lauver M. Lukacher A.(2018).Brincidofovir BCV) demonstrates antiviral activity against murine polyomavirus (MuPyV) in a mouse model of acute infection [SA\u2010PO642]. Kidney Week 2018 San Diego CA."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2004.06.008"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18842-0"},{"key":"e_1_2_6_14_1","unstructured":"US National Library of Medicine. (2019).Study Record Detail: The AdAPT Trial; Adenovirus After Allogeneic Pediatric Transplantation (NCT03339401).ClinicalTrials.gov. Registry. Retrieved fromhttps:\/\/clinicaltrials.gov\/ct2\/show\/NCT03339401"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051586"},{"key":"e_1_2_6_16_1","unstructured":"Gilead Sciences Inc. (2010).Vistide (cidofovir injection) Full Prescribing Information. Foster City CA. Retrieved fromhttps:\/\/www.gilead.com\/~\/media\/files\/pdfs\/medicines\/other\/vistide\/vistide.pdf"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.594"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5061","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.5061","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:44:14Z","timestamp":1760042654000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.5061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/bmc.5061"],"URL":"https:\/\/doi.org\/10.1002\/bmc.5061","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"assertion":[{"value":"2020-10-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5061"}}