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Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain \u03b2-lactams (e.g., imipenem) and \u03b2-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used\n                      <jats:italic>in vitro<\/jats:italic>\n                      media are known. We aimed to determine the thermal stability of 10 \u03b2-lactams and 3 BLIs via LC-MS\/MS in cation-adjusted Mueller Hinton broth at 25 and 36\u00b0C as well as agar at 4 and 37\u00b0C, and in water at \u221220, 4, and 25\u00b0C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)\/agar, degradation half-lives were 16.9\/21.8 h for imipenem, 20.7\/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1\/71.6 h for cefsulodin, 40.6\/57.9 h for doripenem, 46.5\/64.6 h for meropenem, 50.8\/97.7 h for cefepime, 61.5\/99.5 h for piperacillin, and &gt;120 h for all other compounds. Broth stability decreased at higher pH. All drugs were \u226590% stable for 72 h in agar at 4\u00b0C. Degradation half-lives in water at 25\u00b0C were &gt;200 h for all drugs except imipenem (14.7 h, at 1,000 mg\/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within \u00b131% of their target concentration. This study provides comprehensive stability data on \u03b2-lactams and BLIs in relevant\n                      <jats:italic>in vitro<\/jats:italic>\n                      media using LC-MS\/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of \u03b2-lactamase-related degradation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01399-23","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T09:00:51Z","timestamp":1707382851000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Comprehensive stability analysis of 13 \u03b2-lactams and \u03b2-lactamase inhibitors in\n                    <i>in vitro<\/i>\n                    media, and novel supplement dosing strategy to mitigate thermal drug degradation"],"prefix":"10.1128","volume":"68","author":[{"given":"Jieqiang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhi","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-246X","authenticated-orcid":true,"given":"Bartolome","family":"Moya","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda and Unidad de investigaci\u00f3n, Hospital Universitario Son Espases, Instituto de investigaci\u00f3n Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa R. 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