{"title":"液相色谱-电喷雾串联质谱联用测定大鼠血浆中AZD5462及其代谢物","authors":"Congyao You, Yan Zhang, Dece Kong, Tieyi Yang","doi":"10.1002/bmc.70095","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>AZD5462, a human RXFP1 agonist, which is undergoing clinical development for the treatment of heart failure. The aim of this study was to develop an ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of AZD5462 in rat plasma. After precipitated with acetonitrile, the sample was analyzed on a BEH C<sub>18</sub> column using 0.1% formic acid and acetonitrile as mobile phase with a gradient elution at 40°C within 2 min. The assay showed excellent linearity in the range of 0.1–1000 ng/mL with the correlation coefficient more than 0.995. The precision, accuracy, matrix effect, recovery, and stability met all requirements for the quantitation in plasma samples. The validated method has been further applied to the pharmacokinetic study of AZD5462 in rats. In addition, the metabolism of AZD5462 in rat was investigated by a liquid chromatography-high resolution mass spectrometry. In rat liver microsomes, four metabolites were identified based on their accurate mass and fragment ions. In rat plasma, one glucuronide conjugate was identified. The metabolic pathways of AZD5462 include oxygenation and glucuronidation. This study is the first report on the pharmacokinetics and metabolism of AZD5462, which would provide insights into the effectiveness and toxicity of this drug candidate.</p>\n </div>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 6","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry for the Determination and Identification of AZD5462 and Its Metabolites in Rat Plasma\",\"authors\":\"Congyao You, Yan Zhang, Dece Kong, Tieyi Yang\",\"doi\":\"10.1002/bmc.70095\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>AZD5462, a human RXFP1 agonist, which is undergoing clinical development for the treatment of heart failure. The aim of this study was to develop an ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of AZD5462 in rat plasma. After precipitated with acetonitrile, the sample was analyzed on a BEH C<sub>18</sub> column using 0.1% formic acid and acetonitrile as mobile phase with a gradient elution at 40°C within 2 min. The assay showed excellent linearity in the range of 0.1–1000 ng/mL with the correlation coefficient more than 0.995. The precision, accuracy, matrix effect, recovery, and stability met all requirements for the quantitation in plasma samples. The validated method has been further applied to the pharmacokinetic study of AZD5462 in rats. In addition, the metabolism of AZD5462 in rat was investigated by a liquid chromatography-high resolution mass spectrometry. In rat liver microsomes, four metabolites were identified based on their accurate mass and fragment ions. In rat plasma, one glucuronide conjugate was identified. The metabolic pathways of AZD5462 include oxygenation and glucuronidation. This study is the first report on the pharmacokinetics and metabolism of AZD5462, which would provide insights into the effectiveness and toxicity of this drug candidate.</p>\\n </div>\",\"PeriodicalId\":8861,\"journal\":{\"name\":\"Biomedical Chromatography\",\"volume\":\"39 6\",\"pages\":\"\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Chromatography\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70095\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Chromatography","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70095","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry for the Determination and Identification of AZD5462 and Its Metabolites in Rat Plasma
AZD5462, a human RXFP1 agonist, which is undergoing clinical development for the treatment of heart failure. The aim of this study was to develop an ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of AZD5462 in rat plasma. After precipitated with acetonitrile, the sample was analyzed on a BEH C18 column using 0.1% formic acid and acetonitrile as mobile phase with a gradient elution at 40°C within 2 min. The assay showed excellent linearity in the range of 0.1–1000 ng/mL with the correlation coefficient more than 0.995. The precision, accuracy, matrix effect, recovery, and stability met all requirements for the quantitation in plasma samples. The validated method has been further applied to the pharmacokinetic study of AZD5462 in rats. In addition, the metabolism of AZD5462 in rat was investigated by a liquid chromatography-high resolution mass spectrometry. In rat liver microsomes, four metabolites were identified based on their accurate mass and fragment ions. In rat plasma, one glucuronide conjugate was identified. The metabolic pathways of AZD5462 include oxygenation and glucuronidation. This study is the first report on the pharmacokinetics and metabolism of AZD5462, which would provide insights into the effectiveness and toxicity of this drug candidate.
期刊介绍：
Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
