Constantin Lier, Alexander Dejaco, Alexander Kratzer, Martin G Kees, Frieder Kees, Christoph Dorn
{"title":"通过超滤测定抗生素的游离血清浓度:对实验变量的广泛评估。","authors":"Constantin Lier, Alexander Dejaco, Alexander Kratzer, Martin G Kees, Frieder Kees, Christoph Dorn","doi":"10.1080/17576180.2024.2365526","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics.<b>Materials & methods:</b> Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000 × g).<b>Results:</b> Generally, at 10,000 × g the unbound fraction (<i>f</i><sub>u</sub>) decreased with increasing molecular weight, and was lower at 22°C. In unbuffered serum, the <i>f</i><sub>u</sub> of flucloxacillin or valproic acid was increased, that of basic or amphoteric drugs considerably decreased. Comparable results were obtained using phosphate or HEPES buffer except for drugs which form metal chelate complexes.<b>Conclusion:</b> Maintaining a physiological pH is more important than strictly maintaining body temperature.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389746/pdf/","citationCount":"0","resultStr":"{\"title\":\"Free serum concentrations of antibiotics determined by ultrafiltration: extensive evaluation of experimental variables.\",\"authors\":\"Constantin Lier, Alexander Dejaco, Alexander Kratzer, Martin G Kees, Frieder Kees, Christoph Dorn\",\"doi\":\"10.1080/17576180.2024.2365526\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Aim:</b> To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics.<b>Materials & methods:</b> Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000 × g).<b>Results:</b> Generally, at 10,000 × g the unbound fraction (<i>f</i><sub>u</sub>) decreased with increasing molecular weight, and was lower at 22°C. In unbuffered serum, the <i>f</i><sub>u</sub> of flucloxacillin or valproic acid was increased, that of basic or amphoteric drugs considerably decreased. Comparable results were obtained using phosphate or HEPES buffer except for drugs which form metal chelate complexes.<b>Conclusion:</b> Maintaining a physiological pH is more important than strictly maintaining body temperature.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389746/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17576180.2024.2365526\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/23 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17576180.2024.2365526","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Free serum concentrations of antibiotics determined by ultrafiltration: extensive evaluation of experimental variables.
Aim: To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics.Materials & methods: Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000 × g).Results: Generally, at 10,000 × g the unbound fraction (fu) decreased with increasing molecular weight, and was lower at 22°C. In unbuffered serum, the fu of flucloxacillin or valproic acid was increased, that of basic or amphoteric drugs considerably decreased. Comparable results were obtained using phosphate or HEPES buffer except for drugs which form metal chelate complexes.Conclusion: Maintaining a physiological pH is more important than strictly maintaining body temperature.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.