The Effect of Yinchenhao Decoction on the Pharmacokinetic Profile of Futibatinib by HPLC-MS/MS

IF 2.5 4区工程技术 Q3 CHEMISTRY, ANALYTICAL

Separations Pub Date : 2024-07-11 DOI:10.3390/separations11070213

Chunfu Wang, Songmao Liang, Jiachen Xu, Yingfan Zhai, Jianghui Chen, Xiangjun Qiu

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引用次数: 0

Abstract

Futibatinib is an excellent fibroblast growth factor receptor 1–4 (FGFR 1–4) inhibitor that exhibits selective anti-tumor activeness against FGFR-deregulated tumors. A new high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique for the quantitative analysis of futibatinib in beagle dog plasma was developed, and the effect of Yinchenhao decoction (YCHD) on the pharmacokinetics of futibatinib was evaluated. After processing plasma samples with ethyl acetate extraction in the alkaline condition of sodium carbonate, a C18 column (4.6 mm × 150, 5 μm) was used to accomplish the separation of futibatinib and ripretinib (internal standard, ISTD), with the mobile phase consisting of methanol and 0.1% formic acid in water (60:40). The scanning method adopted a multiple reaction monitoring (MRM) mode with positive ion detection through the triple quadrupole mass spectrometer. The ion transitions for futibatinib and IS were m/z 419.20 → 296.15 and m/z 510.36 → 417.00, respectively. Futibatinib displayed excellent linearity in the range of 1–200 ng/mL. Neither inter-day nor intra-day precision exceeded 6.3%. The %RE values for accuracy ranged from −3.1% to 0.9%. The recovery, stability, and matrix effect of futibatinib also complied with the guidelines for the validation of quantitative analysis methods for biological samples in the 2020 edition of the Chinese Pharmacopoeia. In combination with YCHD, the Cmax of futibatinib increased by 40.84% compared to futibatinib dosage alone., and the AUC(0–t) and AUC(0–∞) of futibatinib increased by 78.06% and 82.71%, respectively. The Vd and CL of futibatinib were reduced by 20.05% and 40.85%, respectively. T1/2 was extended from 3.88 h to 5.26 h. The results indicated that YCHD could affect the pharmacokinetics of futibatinib and increase the plasma exposure of futibatinib. If YCHD is administered along with futibatinib, this study gives a first impression how pharmacokinetics and toxicokinetics would change.

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通过HPLC-MS/MS分析银翘解毒片对福替尼药代动力学特征的影响

福替巴替尼是一种优良的成纤维细胞生长因子受体1-4（FGFR 1-4）抑制剂，对FGFR调控的肿瘤具有选择性抗肿瘤活性。本研究开发了一种新型高效液相色谱-串联质谱（HPLC-MS/MS）技术，用于定量分析小猎犬血浆中的氟替尼，并评估了银翘解毒片（YCHD）对氟替尼药代动力学的影响。血浆样品在碳酸钠碱性条件下经乙酸乙酯萃取处理后，采用C18色谱柱（4.6 mm×150, 5 μm）分离富替巴替尼和瑞培替尼（内标物，ISTD），流动相为甲醇和0.1%甲酸水溶液（60:40）。扫描方法采用多反应监测（MRM）模式，通过三重四极杆质谱仪进行正离子检测。富替替尼和IS的离子跃迁分别为m/z 419.20 → 296.15和m/z 510.36 → 417.00。福替替尼在 1-200 纳克/毫升范围内显示出良好的线性关系。日间和日内精密度均未超过 6.3%。准确度的%RE值介于-3.1%至0.9%之间。该方法的回收率、稳定性和基质效应均符合《中国药典》2020年版生物样品定量分析方法验证指南的要求。与YCHD联用，与单用相比，氟替替尼的Cmax增加了40.84%，AUC(0-t)和AUC(0-∞)分别增加了78.06%和82.71%。福替替尼的Vd和CL分别降低了20.05%和40.85%。结果表明，YCHD可影响福替替尼的药代动力学，增加福替替尼的血浆暴露量。如果YCHD与福替替尼同时给药，本研究将给出药代动力学和毒代动力学如何变化的初步印象。

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来源期刊

Separations Chemistry-Analytical Chemistry

CiteScore

3.00

自引率

15.40%

发文量

342

审稿时长

12 weeks

期刊介绍： Separations (formerly Chromatography, ISSN 2227-9075, CODEN: CHROBV) provides an advanced forum for separation and purification science and technology in all areas of chemical, biological and physical science. It publishes reviews, regular research papers and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. There are, in addition, unique features of this journal: Manuscripts regarding research proposals and research ideas will be particularly welcomed. Electronic files and software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. Manuscripts concerning summaries and surveys on research cooperation and projects (that are funded by national governments) to give information for a broad field of users. The scope of the journal includes but is not limited to: Theory and methodology (theory of separation methods, sample preparation, instrumental and column developments, new separation methodologies, etc.) Equipment and techniques, novel hyphenated analytical solutions (significantly extended by their combination with spectroscopic methods and in particular, mass spectrometry) Novel analysis approaches and applications to solve analytical challenges which utilize chromatographic separations as a key step in the overall solution Computational modelling of separations for the purpose of fundamental understanding and/or chromatographic optimization