Quantitation of anacetrapib in human and animal adipose by liquid chromatography with mass spectrometric detection.

IF 1.9 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-08-09 DOI:10.1080/17576180.2024.2376427
Wei Fang, Cynthia M Chavez-Eng, Ryan W Lutz, Hankun Li, Jessica Schlegel, Brad Roadcap, James Schiller, Eric Woolf
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Abstract

Cholesteryl ester transfer protein (CETP) inhibitor is a target for both lowering low-density lipoproteins and raising high-density lipoproteins. Anacetrapib was the lead compound in our cholesteryl ester transfer protein inhibitor program. Preclinical studies were initiated to support the safety of anacetrapib deposition in adipose tissue, followed by a clinical trial to evaluate the effects of anacetrapib in people with vascular disease. An ultra-high performance liquid chromatography/tandem mass spectrometry method was developed to determine tissue anacetrapib concentrations in the adipose of three animal species and humans. The assays were validated in the concentration ranges of 5-5000 ng/ml and 0.1-100 μg/ml. The anacetrapib concentrations in adipose tissue from preclinical and clinical studies were determined.

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利用液相色谱-质谱检测法定量分析人类和动物脂肪中的安赛拉哌。
胆固醇酯转移蛋白 (CETP) 抑制剂是降低低密度脂蛋白和提高高密度脂蛋白的靶点。Anacetrapib 是我们胆固醇酯转移蛋白抑制剂项目的先导化合物。我们启动了临床前研究,以支持 Anacetrapib 在脂肪组织中沉积的安全性,随后进行了临床试验,以评估 Anacetrapib 对血管疾病患者的影响。我们开发了一种超高效液相色谱/串联质谱法,用于测定三种动物和人体脂肪组织中的安非他酮浓度。该方法在 5-5000 纳克/毫升和 0.1-100 微克/毫升的浓度范围内进行了验证。测定了临床前和临床研究中脂肪组织中的阿那曲拉比浓度。
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来源期刊
Bioanalysis
Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
3.30
自引率
16.70%
发文量
88
审稿时长
2 months
期刊介绍: Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.
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