{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:08:49Z","timestamp":1788239329062,"version":"build-2803163510"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To develop and validate an UPLC\u2013MS\/MS assay for simultaneous determination of the total concentration of ceftazidime, ciprofloxacin, flucloxacillin, piperacillin, tazobactam, sulfamethoxazole, N-acetyl sulfamethoxazole and trimethoprim, and the protein-unbound concentration of flucloxacillin, in human plasma to be used for research and clinical practice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Sample pretreatment included protein precipitation with methanol. For the measurement of protein-unbound flucloxacillin, ultrafiltration was performed at physiological temperature. For all compounds, a stable isotopically labelled internal standard was used. Reliability of the results was assessed by participation in an international quality control programme.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The assay was successfully validated according to the EMA guidelines over a concentration range of 0.5\u2013100\u2005mg\/L for ceftazidime, 0.05\u201310\u2005mg\/L for ciprofloxacin, 0.4\u2013125\u2005mg\/L for flucloxacillin, 0.2\u201360\u2005mg\/L for piperacillin, 0.15\u201330\u2005mg\/L for tazobactam, 1\u2013200\u2005mg\/L for sulfamethoxazole and N-acetyl sulfamethoxazole, 0.05\u201310\u2005mg\/L for trimethoprim and 0.10\u201350\u2005mg\/L for unbound flucloxacillin. For measurement of total concentrations, the within- and between-day accuracy ranged from 90.0% to 109%, and 93.4% to 108%, respectively. Within- and between-day precision (variation coefficients, CVs) ranged from 1.70% to 11.2%, and 0.290% to 5.30%, respectively. For unbound flucloxacillin, within-day accuracy ranged from 103% to 106% and between-day accuracy from 102% to 105%. The within- and between-day CVs ranged from 1.92% to 7.11%. Results of the international quality control programme showed that the assay is reliable.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The method provided reliable, precise and accurate measurement of seven commonly prescribed antibiotics, including the unbound concentration of flucloxacillin. This method is now routinely applied in research and clinical practice.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae047","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T16:08:02Z","timestamp":1709136482000},"page":"883-890","source":"Crossref","is-referenced-by-count":5,"title":["Development and validation of an UPLC\u2013MS\/MS assay for the simultaneous quantification of seven commonly used antibiotics in human plasma and its application in therapeutic drug monitoring"],"prefix":"10.1093","volume":"79","author":[{"given":"Xin Meng","family":"Mekking","sequence":"first","affiliation":[{"name":"School of Pharmacy, Utrecht University , Leuvenlaan 4, 3584 CE, Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Velthoven-Graafland","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marga J A","family":"Teulen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-725X","authenticated-orcid":false,"given":"Roger J M","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey H M","family":"te Brake","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4524-9892","authenticated-orcid":false,"given":"Nynke G L","family":"Jager","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Medical Innovation, Radboud University Medical Centre , Geert Grooteplein Zuid 10, 6525 GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"2024040202344808900_dkae047-B1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2165\/00003088-200241100-00004","article-title":"Clinical role of protein binding of quinolones","volume":"41","author":"Bergogne-B\u00e9r\u00e9zin","year":"2002","journal-title":"Clin Pharmacokinet"},{"key":"2024040202344808900_dkae047-B2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/AAC.32.3.298","article-title":"Effect of protein binding on serum bactericidal activities of ceftazidime and cefoperazone in healthy volunteers","volume":"32","author":"Lam","year":"1988","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202344808900_dkae047-B3","doi-asserted-by":"crossref","first-page":"6165","DOI":"10.1128\/AAC.00951-13","article-title":"Protein binding of \u03b2-lactam antibiotics in critically ill patients: can we successfully predict unbound concentrations?","volume":"57","author":"Wong","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2024040202344808900_dkae047-B4","doi-asserted-by":"crossref","first-page":"452","DOI":"10.2215\/CJN.10741011","article-title":"Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT","volume":"7","author":"Bauer","year":"2012","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024040202344808900_dkae047-B5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/FTD.0000000000000602","article-title":"Measuring unbound versus total piperacillin concentrations in plasma of critically ill patients: methodological issues and relevance","volume":"41","author":"Colman","year":"2019","journal-title":"Ther Drug Monit"},{"key":"2024040202344808900_dkae047-B6","author":"European Medicines Agency"},{"key":"2024040202344808900_dkae047-B7","author":"Food and Drug Administration"},{"key":"2024040202344808900_dkae047-B8","doi-asserted-by":"crossref","first-page":"446.e1","DOI":"10.1016\/j.cmi.2021.06.039","article-title":"A meta-analysis of protein binding of flucloxacillin in healthy volunteers and hospitalized patients","volume":"28","author":"Wallenburg","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2024040202344808900_dkae047-B9","first-page":"340","volume-title":"Yaffe and Aranda\u2019s Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice","author":"Burger","year":"2021","edition":"5th edn"},{"key":"2024040202344808900_dkae047-B10","volume-title":"Guideline on Bioanalytical Method Validation","author":"European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP)","year":"2009"},{"key":"2024040202344808900_dkae047-B11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jchromb.2017.08.004","article-title":"Determination of protein-unbound, active rifampicin in serum by ultrafiltration and ultra performance liquid chromatography with UV detection. A method suitable for standard and high doses of rifampicin","volume":"1063","author":"van Ewijk-Beneken Kolmer","year":"2017","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2024040202344808900_dkae047-B12","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1093\/jac\/dkab314","article-title":"High unbound flucloxacillin fraction in critically ill patients","volume":"76","author":"Wallenburg","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2024040202344808900_dkae047-B13","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s40262-022-01113-6","article-title":"An integral pharmacokinetic analysis of piperacillin and tazobactam in plasma and urine in critically ill patients","volume":"61","author":"Wallenburg","year":"2022","journal-title":"Clin Pharmacokinet"},{"key":"2024040202344808900_dkae047-B14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/jac\/dkaa445","article-title":"First international quality control programme for laboratories measuring antimicrobial drugs to support dose individualization in critically ill patients","volume":"76","author":"Wallenburg","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"2024040202344808900_dkae047-B15","doi-asserted-by":"crossref","DOI":"10.1093\/jac\/dkae092","article-title":"Influence of ultrafiltration conditions on the measurement of unbound drug concentrations: flucloxacillin as an example. Submitted for publication. 2023","author":"Jager","year":"2024","journal-title":"Journal of Antimicrobial Chemotherapy"},{"key":"2024040202344808900_dkae047-B16","doi-asserted-by":"crossref","first-page":"113273","DOI":"10.1016\/j.jpba.2020.113273","article-title":"A liquid chromatography-tandem mass spectrometry platform for the routine therapeutic drug monitoring of 14 antibiotics: application to critically ill pediatric patients","volume":"186","author":"Barco","year":"2020","journal-title":"J Pharm Biomed Anal"},{"key":"2024040202344808900_dkae047-B17","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cca.2017.03.009","article-title":"Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of \u03b2-lactam antibiotic concentration in human plasma","volume":"468","author":"Rigo-Bonnin","year":"2017","journal-title":"Clin Chim Acta"},{"key":"2024040202344808900_dkae047-B18","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.cca.2020.11.001","article-title":"LC-MS\/MS method for nine different antibiotics","volume":"511","author":"Rehm","year":"2020","journal-title":"Clin Chim Acta"},{"key":"2024040202344808900_dkae047-B19","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.jchromb.2011.03.001","article-title":"Simultaneous determination of eight \u03b2-lactam antibiotics in human serum by liquid chromatography-tandem mass spectrometry","volume":"879","author":"Ohmori","year":"2011","journal-title":"J Chromatogr B"},{"key":"2024040202344808900_dkae047-B20","doi-asserted-by":"crossref","first-page":"112904","DOI":"10.1016\/j.jpba.2019.112904","article-title":"Simultaneous determination of eight \u03b2-lactam antibiotics in human plasma and cerebrospinal fluid by liquid chromatography coupled to tandem mass spectrometry","volume":"178","author":"Bellouard","year":"2020","journal-title":"J Pharm Biomed Anal"},{"key":"2024040202344808900_dkae047-B21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/FTD.0000000000000570","article-title":"Simultaneous quantification of nine antimicrobials by LC-MS\/MS for therapeutic drug monitoring in critically ill patients","volume":"41","author":"Neugebauer","year":"2019","journal-title":"Ther Drug Monit"},{"key":"2024040202344808900_dkae047-B22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jchromb.2014.11.034","article-title":"Ultrafast quantification of \u03b2-lactam antibiotics in human plasma using UPLC\u2013MS\/MS","volume":"978\u2013979","author":"Carlier","year":"2015","journal-title":"J Chromatogr B"},{"key":"2024040202344808900_dkae047-B23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/rcm.1790","article-title":"Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography\/mass spectrometry: necessity or not?","volume":"19","author":"Stokvis","year":"2005","journal-title":"Rapid Commun Mass Spectrom"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/4\/883\/57130749\/dkae047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/79\/4\/883\/57130749\/dkae047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T02:36:19Z","timestamp":1712025379000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/79\/4\/883\/7615550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2,28]]},"published-print":{"date-parts":[[2024,4,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkae047","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2024,2,28]]}}}