{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T05:01:29Z","timestamp":1773982889239,"version":"3.50.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"EDCTP2","award":["ASAAP RIA2017MC-2022"],"award-info":[{"award-number":["ASAAP RIA2017MC-2022"]}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU 03.709"],"award-info":[{"award-number":["TTU 03.709"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005711","name":"Universit\u00e4t Hamburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Malaria still poses a significant burden on global health, with millions of cases reported annually and rising resistance to current treatments, emphasizing the need for new therapeutic strategies. Fosmidomycin, initially recognized for its antibacterial properties, has emerged as a promising candidate in the fight against malaria.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study, a sensitive and robust LC\u2013MS\/MS method for quantifying fosmidomycin in human and rat plasma was developed and validated. Plasma samples were prepared using a simple protein precipitation method with 10% trichloroacetic acid (TCA). The assay featured a rapid run time of 5\u00a0min, and validation was performed according to the European Medicines Agency's guidelines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The method validation confirmed its selectivity, linearity, accuracy, precision, and stability. Notably, the calibration range was established from 0.25 to 15\u00a0mg\/L, demonstrating improvements over previous methodologies with lower limits of quantification of 0.5\u20131.0\u00a0mg\/L. Using the developed LC\u2013MS\/MS method, plasma samples were analysed from a clinical trial conducted in Gabon, as well as from a pharmacokinetic study involving male Wistar rats, revealing viable pharmacokinetic profiles for fosmidomycin.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These findings confirm the utility of the developed analytical method for supporting the clinical development of fosmidomycin as a potential therapy for malaria.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12936-025-05489-1","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:46:50Z","timestamp":1753444010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and application of an LC\u2013MS\/MS method for quantification of fosmidomycin in human and rat plasma"],"prefix":"10.1186","volume":"24","author":[{"given":"Christoph","family":"Pfaffendorf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keanu D.","family":"Sackmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Mischlinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Claude","family":"Dejon-Agob\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oumou","family":"Ma\u00efga-Ascofar\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebenezer","family":"Ahenkan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ay\u00f4la Akim","family":"Adegnika","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ramharter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Uhl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gert","family":"Fricker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian G.","family":"Wicha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"5489_CR1","volume-title":"World malaria report 2023","author":"WHO","year":"2023","unstructured":"WHO. World malaria report 2023. Geneva: World Health Organization; 2023."},{"key":"5489_CR2","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1038\/s41591-020-1005-2","volume":"26","author":"A Uwimana","year":"2020","unstructured":"Uwimana A, Legrand E, Stokes BH, Ndikumana J-LM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26:1602\u20138.","journal-title":"Nat Med"},{"key":"5489_CR3","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1056\/NEJMoa2101746","volume":"385","author":"B Balikagala","year":"2021","unstructured":"Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385:1163\u201371.","journal-title":"N Engl J Med"},{"key":"5489_CR4","doi-asserted-by":"publisher","first-page":"44","DOI":"10.7164\/antibiotics.33.44","volume":"33","author":"H Kojo","year":"1980","unstructured":"Kojo H, Shigi Y, Nishida M. FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability. J Antibiot. 1980;33:44\u20138.","journal-title":"J Antibiot"},{"key":"5489_CR5","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1128\/AAC.22.4.560","volume":"22","author":"HC Neu","year":"1982","unstructured":"Neu HC, Kamimura T. Synergy of fosmidomycin (FR-31564) and other antimicrobial agents. Antimicrob Agents Chemother. 1982;22:560\u20133.","journal-title":"Antimicrob Agents Chemother"},{"key":"5489_CR6","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1126\/science.285.5433.1573","volume":"285","author":"H Jomaa","year":"1999","unstructured":"Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999;285:1573\u20136.","journal-title":"Science"},{"key":"5489_CR7","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s00436-002-0770-9","volume":"90","author":"J Wiesner","year":"2003","unstructured":"Wiesner J, Borrmann S, Jomaa H. Fosmidomycin for the treatment of malaria. Parasitol Res. 2003;90:71\u20136.","journal-title":"Parasitol Res"},{"key":"5489_CR8","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.2217\/FMB.15.60","volume":"10","author":"JF Fernandes","year":"2015","unstructured":"Fernandes JF, Lell B, Agnandji ST, Obiang RM, Bassat Q, Kremsner PG, et al. Fosmidomycin as an antimalarial drug: a meta-analysis of clinical trials. Future Microbiol. 2015;10:1375\u201390.","journal-title":"Future Microbiol"},{"key":"5489_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.mimet.2006.11.018","volume":"69","author":"A Cheoymang","year":"2007","unstructured":"Cheoymang A, Hudchinton D, Kioy D, Na-Bangchang K. Bioassay for determination of fosmidomycin in plasma and urine: application for pharmacokinetic dose optimisation. J Microbiol Methods. 2007;69:65\u20139.","journal-title":"J Microbiol Methods"},{"key":"5489_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jchromb.2004.04.002","volume":"806","author":"S Bronner","year":"2004","unstructured":"Bronner S, Renault C, Hintz M, Wiesner J, Jomaa H, Monteil H, et al. Determination of fosmidomycin in human serum and urine by capillary electrophoresis. Chromatogr B Analyt Technol Biomed Life Sci. 2004;806:255\u201361.","journal-title":"Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"5489_CR11","unstructured":". https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-bioanalytical-method-validation_en.pdf. Accessed 26 Mar 2024."},{"issue":"S65","key":"5489_CR12","first-page":"11","volume":"42","author":"WS Denney","year":"2015","unstructured":"Denney WS, Duvvuri S, Buckeridge C. Simple, automatic noncompartmental analysis: the PKNCA R package. 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Malar J. 2007;6:70.","journal-title":"Malar J"},{"key":"5489_CR15","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1128\/AAC.21.2.224","volume":"21","author":"T Murakawa","year":"1982","unstructured":"Murakawa T, Sakamoto H, Fukada S, Konishi T, Nishida M. Pharmacokinetics of fosmidomycin, a new phosphonic acid antibiotic. Antimicrob Agents Chemother. 1982;21:224\u201330.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-025-05489-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-025-05489-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-025-05489-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T23:46:38Z","timestamp":1757288798000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-025-05489-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5489"],"URL":"https:\/\/doi.org\/10.1186\/s12936-025-05489-1","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]},"assertion":[{"value":"25 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study conformed to the Declaration of Helsinki and Standard Operating Procedures that meet current regulatory requirements and guidelines laid down by the International Conference on Harmonisation for Good Clinical Practice in Clinical Studies. The clinical trial was approved by the relevant Independent Ethics Committees, national Institutional Review Boards, and local regulatory authorities at Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9 (CERMEL) (Lambar\u00e9n\u00e9, Gabon). The study protocol was registered online before start of recruitment into this clinical trial (pactr.samrc.ac.za, PACTR202008909968293). All animal studies were approved by the Animal Care and Use committees from Regierungspr\u00e4sidium Karlsruhe (Karlsruhe, Germany; reference number 35-9185.81\/G-223\/21).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"243"}}