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已发表论文
一种用于测定大鼠血浆中 I-BET151 的 HPLC-MS/MS 方法的开发与验证及其在药代动力学研究中的应用
Authors Wang S
Received 29 May 2025
Accepted for publication 14 August 2025
Published 25 September 2025 Volume 2025:19 Pages 8679—8689
DOI https://doi.org/10.2147/DDDT.S540415
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Shengnan Wang
Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China
Correspondence: Shengnan Wang, Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Number 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of China, Email wangshengnansy163@163.com
Propose: A bromodomain and extra-terminal domain inhibitor (I-BET151) is effective in treating chronic graft-versus-host disease and has been extensively studied in recent years. However, there is limited research on the pharmacokinetics of I-BET151, especially the lack of methods for determining the concentration of I-BET151 in vivo. Therefore, the purpose of this study is to establish an HPLC-MS/MS method for determining the plasma concentration of I-BET151 and use it for pharmacokinetic study in rats.
Methods: The chromatographic column is a Poroshell 120EC-C18 column (50 mm × 4.6 mm, 2.7 μm). The mobile phase consists of water containing 20 mmol ammonium acetate and 0.1% formic acid, and methanol containing 0.1% formic acid, with a flow rate of 0.6 mL/min. The extraction of I-BET151 is liquid–liquid extraction, and the extraction solvent is ether:dichloromethane=2:3. The HPLC-MS/MS method was validated based on the guidelines of quantitative methods for biological samples in the Chinese Pharmacopoeia, including specificity, standard curve, lower limit of quantification, residual effects, precision, recovery rate, matrix effects, stability, etc.
Results: The results showed that the established method met the requirements of methodological validation standards and could be used for pharmacokinetic studies of I-BET151. The pharmacokinetic results displayed that the half-life of oral and intravenous administration of I-BET151 was 4.3 h and 3.1 h, respectively. The oral bioavailability was about 60%, indicating that I-BET151 had a high oral bioavailability and appropriate half-life, demonstrating good clinical application prospects.
Keywords: HPLC-MS/MS, method validation, I-BET151, pharmacokinetics, bioavailability
Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China
Correspondence: Shengnan Wang, Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Number 44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning, 110042, People’s Republic of China, Email wangshengnansy163@163.com
Propose: A bromodomain and extra-terminal domain inhibitor (I-BET151) is effective in treating chronic graft-versus-host disease and has been extensively studied in recent years. However, there is limited research on the pharmacokinetics of I-BET151, especially the lack of methods for determining the concentration of I-BET151 in vivo. Therefore, the purpose of this study is to establish an HPLC-MS/MS method for determining the plasma concentration of I-BET151 and use it for pharmacokinetic study in rats.
Methods: The chromatographic column is a Poroshell 120EC-C18 column (50 mm × 4.6 mm, 2.7 μm). The mobile phase consists of water containing 20 mmol ammonium acetate and 0.1% formic acid, and methanol containing 0.1% formic acid, with a flow rate of 0.6 mL/min. The extraction of I-BET151 is liquid–liquid extraction, and the extraction solvent is ether:dichloromethane=2:3. The HPLC-MS/MS method was validated based on the guidelines of quantitative methods for biological samples in the Chinese Pharmacopoeia, including specificity, standard curve, lower limit of quantification, residual effects, precision, recovery rate, matrix effects, stability, etc.
Results: The results showed that the established method met the requirements of methodological validation standards and could be used for pharmacokinetic studies of I-BET151. The pharmacokinetic results displayed that the half-life of oral and intravenous administration of I-BET151 was 4.3 h and 3.1 h, respectively. The oral bioavailability was about 60%, indicating that I-BET151 had a high oral bioavailability and appropriate half-life, demonstrating good clinical application prospects.
Keywords: HPLC-MS/MS, method validation, I-BET151, pharmacokinetics, bioavailability