{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:14:43Z","timestamp":1786947283302,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Small Animal Practice"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Solutions of methadone diluted in 0.9% NaCl, and methadone\u2013lidocaine\u2013ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4\u00b0C and protected from light, were maintained over 10\u2009days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240\u2009hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet\/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone\u2013lidocaine\u2013ketamine with Hartmann's solution at 4\u00b0C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone\u2013lidocaine\u2013ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone\u2013lidocaine\u2013ketamine components retained acceptable stability (&lt;10%\u00a0degradation) for at least 48\u2009hours following preparation, irrespective of diluent or storage conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Significance<\/jats:title><jats:p>Regardless of the diluent or storage method, methadone\u2013lidocaine\u2013ketamine solutions degrade over time, but this only becomes clinically significant after 48\u2009hours. Solutions of 1\u00a0mg\/ml methadone in 0.9% NaCl are stable for at least 10\u2009days under storage conditions likely to be encountered in general practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jsap.13490","type":"journal-article","created":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T04:53:44Z","timestamp":1646456024000},"page":"526-531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stability of dilutions of methadone alone, and in combination with lidocaine and ketamine"],"prefix":"10.1111","volume":"63","author":[{"given":"A.","family":"Gomez","sequence":"first","affiliation":[{"name":"Southern Counties Veterinary Specialists  Ringwood Hampshire BH24 3JW UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Al\u2010Tannak","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow G4 0RE UK"},{"name":"Department of Pharmaceutical Chemistry Kuwait University  12037 Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Auckburally","sequence":"additional","affiliation":[{"name":"Southern Counties Veterinary Specialists  Ringwood Hampshire BH24 3JW UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Watson","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow G4 0RE UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Southern Counties Veterinary Specialists  Ringwood Hampshire BH24 3JW UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2010.05.029"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-020-02735-3"},{"key":"e_1_2_5_4_1","first-page":"129","article-title":"Stability testing of pharmaceutical product","volume":"02","author":"Bajaj S.","year":"2012","journal-title":"Journal of Applied Pharmaceutical Science"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/ejhpharm-2019-001976"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-014-0299-z"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.5326\/JAAHA-MS-6442"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.4097\/kjae.2015.68.5.476"},{"key":"e_1_2_5_9_1","first-page":"1048","article-title":"d\u2010Methadone blocks morphine tolerance and N\u2010methyl\u2010d\u2010aspartate\u2010induced hyperalgesia","volume":"289","author":"Davis A. 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