Development and validation of an LC-MS/MS method for simultaneous determination of XZP-3287(bireociclib) and its metabolites in human plasma, and its clinical pharmacokinetics application

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-05-16 DOI:10.1016/j.jchromb.2025.124658

Bohan Liang , Yanjie Li , Lingmei Xu , Li Wang , Quankun Zhuang , Shiqi Dong , Huirong Fan

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引用次数: 0

Abstract

XZP-3287(bireociclib) is a novel and selective inhibitor of the cell cyclin-dependent kinases 4/6 (CDK4/6), which is primarily employed for the treatment of breast cancer in clinical trials. In this study, a novel and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of XZP-3287 and its metabolites XZP-5286, XZP-3584 and XZP-5736 in human plasma in accordance with international conference on harmonization of technical requirements for registration of Pharmaceuticals for Human use (ICH) guideline R3 (M10) guideline. The multiple reaction monitoring mode (MRM) of mass spectrometer was used and all compounds were monitored in electrospray ionization (ESI+) mode. The correlation coefficients (R²) of all calibration curves for linear regression were greater than 0.99. The intra- and inter-day precision of XZP-3287 and its metabolites XZP-5286, XZP-3584 and XZP-5736 were determined to be 5.2 %–5.5 %, 14.9 %–10.1 %, 6.9 %–13.8 % and 7.3 %–5.6 %, and their accuracy were determined to be 5.2 %–6.0 % 6.9 %–4.4 %, 11.1 %–5.0 % and 7.4 %–5.6 %, respectively. In conclusion, a method for the simultaneous detection of the pharmacokinetic profiles of XZP-3287 and its metabolites in human plasma had been successfully developed. The results demonstrated the efficacy, sensitivity, and reliability of this method

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LC-MS/MS同时测定人血浆中XZP-3287（bireociclib）及其代谢物的方法建立与验证及其临床药代动力学应用

XZP-3287（bireociclib）是一种新型的选择性细胞周期蛋白依赖性激酶4/6 （CDK4/6）抑制剂，主要用于乳腺癌的临床治疗。本研究按照国际人用药品注册技术要求协调会议（ICH）指南R3 （M10）指南的要求，建立了一种新型、灵敏的液相色谱-串联质谱（LC-MS/MS）同时测定人血浆中XZP-3287及其代谢产物XZP-5286、XZP-3584和XZP-5736的方法，并进行了验证。采用质谱仪多反应监测模式（MRM），所有化合物均采用电喷雾电离（ESI+）模式监测。所有线性回归校正曲线的相关系数R2均大于0.99。XZP-3287及其代谢物XZP-5286、XZP-3584和XZP-5736的日内、日间精密度分别为5.2% ~ 5.5%、14.9% ~ 10.1%、6.9% ~ 13.8%和7.3% ~ 5.6%，准确度分别为5.2% ~ 6.0%、6.9% ~ 4.4%、11.1% ~ 5.0%和7.4% ~ 5.6%。总之，建立了同时检测XZP-3287及其代谢物在人血浆中药动学特征的方法。结果证明了该方法的有效性、灵敏度和可靠性

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.