{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:19:04Z","timestamp":1784589544454,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Ministry of Health &amp; Welfare","doi-asserted-by":"publisher","award":["HF20C0002"],"award-info":[{"award-number":["HF20C0002"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Ministry of Health &amp; Welfare","doi-asserted-by":"publisher","award":["2018R1A6A1A03025108"],"award-info":[{"award-number":["2018R1A6A1A03025108"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"Ministry of Education","doi-asserted-by":"publisher","award":["HF20C0002"],"award-info":[{"award-number":["HF20C0002"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2018R1A6A1A03025108"],"award-info":[{"award-number":["2018R1A6A1A03025108"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Fund of The Catholic University of Korea","award":["HF20C0002"],"award-info":[{"award-number":["HF20C0002"]}]},{"name":"Research Fund of The Catholic University of Korea","award":["2018R1A6A1A03025108"],"award-info":[{"award-number":["2018R1A6A1A03025108"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: We developed and validated a robust and simple LC\u2013MS\/MS method for the simultaneous quantification of amoxicillin and clavulanate in human plasma relative to previously reported methods. Methods: Amoxicillin; clavulanate; and an internal standard, 4-hydroxytolbutamide, in human K2-EDTA plasma, were deproteinized with acetonitrile and then subjected to back-extraction using distilled water\u2013dichloromethane. Separation was performed on a Poroshell 120 EC-C18 column with a mobile-phase gradient comprising 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.5 mL\/min within 6.5 min. The negative electrospray ionization modes were utilized to monitor the transitions of m\/z 363.9\u2192223.1 (amoxicillin), m\/z 198.0\u2192135.8 (clavulanate), and m\/z 285.0\u2192185.8 (4-hydroxytolbutamide). Results\/Conclusions: Calibration curves exhibited linear ranges of 10\u201315,000 ng\/mL for amoxicillin (r \u2265 0.9945) and 20\u201310,000 ng\/mL for clavulanate (r \u2265 0.9959). Intra- and inter-day\u2019s coefficients of variation, indicating the precision of the assay, were \u22647.08% for amoxicillin and \u226410.7% for clavulanate, and relative errors in accuracy ranged from \u22121.26% to 10.9% for amoxicillin and from \u22124.41% to 8.73% for clavulanate. All other validation results met regulatory criteria. Partial validation in lithium\u2013heparin, sodium\u2013heparin, and K3-EDTA plasma confirmed applicability in multicenter or large-scale studies. This assay demonstrated itself to be environmentally friendly, as assessed by the Analytical GREEnness (AGREE) tool, and was successfully applied to a clinical pharmacokinetic study of an Augmentin\u00ae IR tablet (250\/125 mg). The inter-individual variabilities in clavulanate exposures (AUCt and Cmax) were significantly greater than in amoxicillin, and they may inform the clinical design of future drug\u2013drug interaction.<\/jats:p>","DOI":"10.3390\/ph18070998","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:07:17Z","timestamp":1751515637000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and Validation of Bioanalytical LC\u2013MS\/MS Method for Pharmacokinetic Assessment of Amoxicillin and Clavulanate in Human Plasma"],"prefix":"10.3390","volume":"18","author":[{"given":"Sangyoung","family":"Lee","sequence":"first","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0295-6119","authenticated-orcid":false,"given":"Da Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabin","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Sun","family":"Min","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Jun","family":"Jo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"},{"name":"Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY 14215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1996-3793","authenticated-orcid":false,"given":"Ui Min","family":"Jerng","sequence":"additional","affiliation":[{"name":"Chungwoo Korean Medicine Hospital, Hanam 12919, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-7187","authenticated-orcid":false,"given":"Soo Kyung","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon 14662, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref_1","unstructured":"Healthcare Big Data Open System (2025). 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