{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:37:41Z","timestamp":1761129461401,"version":"3.41.2"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Global Research in Paediatrics Network of Excellence"},{"name":"National Institute of Health and Care Excellence"},{"name":"European Union's Seventh Framework Programme","award":["608765","261060"],"award-info":[{"award-number":["608765","261060"]}]},{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"crossref","award":["PUTJD 22"],"award-info":[{"award-number":["PUTJD 22"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G1002305","M008665"],"award-info":[{"award-number":["G1002305","M008665"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Penicillins are widely used to treat infections in children; however, the evidence is continuing to evolve in defining the optimal dosing. Modern pediatric pharmacokinetic study protocols frequently favor opportunistic, \u201cscavenged\u201d sampling. This study aimed to develop a small-volume single assay for five major penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modeling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultrahigh-performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin, and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data, the impact of drug degradation on inferences made during pharmacokinetic modeling was evaluated. All evaluated penicillins indicated good stability at room temperature (23 \u00b1 2\u00b0C) over 1 h, remaining in the range of 98 to 103% of the original concentration. More-rapid analyte degradation had already occurred after 4 h, with stability ranging from 68% to 99%. Stability over longer periods declined: degradation of up to 60% was observed with delayed sample processing of up to 24 h. Modeling showed that analyte degradation can lead to a 30% and 28% bias in clearance and volume of distribution, respectively, and falsely show nonlinearity in clearance. Five common penicillins can now be measured in a single low-volume blood sample. Beta-lactam chemical instability in plasma can cause misleading pharmacokinetic modeling results, which could impact upon model-based dosing recommendations and the forthcoming era of beta-lactam therapeutic drug monitoring.<\/jats:p>","DOI":"10.1128\/aac.01540-17","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T15:50:28Z","timestamp":1509378628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Development of a Novel Multipenicillin Assay and Assessment of the Impact of Analyte Degradation: Lessons for Scavenged Sampling in Antimicrobial Pharmacokinetic Study Design"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-8993","authenticated-orcid":false,"given":"Karin","family":"Kipper","sequence":"first","affiliation":[{"name":"Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's University of London, London, United Kingdom"},{"name":"University of Tartu, Institute of Chemistry, Tartu, Estonia"},{"name":"Analytical Services International Ltd., St. George's University of London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte I. 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