Quantification and pharmacokinetic assessment of SB225002 in mouse: a selective non-peptide CXCR2 antagonist.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2026-02-01 Epub Date: 2026-04-10 DOI:10.1080/17576180.2026.2655299

Xinran Wang, Hongbo Miao, Zhijun Liu, Jianguo Sun, Zhenhui Jiang, Liya Ye, Zhengyan Liang, Shouhong Gao, Zhipeng Wang, Wansheng Chen

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引用次数: 0

Abstract

Background: SB225002 was a selective non-peptide antagonist of CXC Chemokine Receptor 2 (CXCR2), but its detection method in mass spectrometry and pharmacokinetic (PK) parameters in mouse were not reported.

Methods and materials: Following methanol-induced protein precipitation and centrifugation, the analyte was separated using an Agilent ZORBAX SB-C18 column (2.1 mm × 100 mm, 3.5 μm, Agilent, MA, USA) with an isocratic mobile phase comprising 25% methanol (phase A) and 75% water containing 0.3% formic acid (phase B). The mobile phase was delivered at a flow rate of 0.3 mL/min. The PK of SB225002 were assessed in a mouse model.

Results: SB225002 demonstrated a strong linear relationship in range of 20.00 to 4000.00 ng/mL, with recovery between 96.9% and 99.6%, and matrix effects ranging from 98.9% to 104.6%. SB225002 demonstrated acceptable short-term, long-term, and freeze-thaw stability, with all other items meeting the requirements. The method was utilized to assess PK of SB225002 in mouse, revealing rapid absorption (t_max: 0.4 ± 0.1 h, mean±SD) and metabolism (t_1/2: 3.4 $\pm$ 2.6 h), along with significant inter-individual variability.

Conclusions: This study successfully developed and validated a UHPLC-MS/MS method to determine SB225002 in mouse plasma and first reported its pharmacokinetic parameters in mouse, potentially facilitating further clinical research.

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小鼠SB225002的定量和药代动力学评估：一种选择性非肽CXCR2拮抗剂。

背景：SB225002是CXC趋化因子受体2 （CXCR2）的选择性非肽拮抗剂，但其质谱检测方法及小鼠药代动力学（PK）参数尚未见报道。方法和材料：甲醇诱导蛋白沉淀和离心后，用Agilent ZORBAX SB-C18色谱柱（2.1 mm × 100 mm, 3.5 μm, Agilent， MA， USA）分离分析物，等温流动相为25%甲醇（A相）和75%含0.3%甲酸的水（B相）。流动相的流速为0.3 mL/min。在小鼠模型中评估SB225002的PK。结果：SB225002在20.00 ~ 4000.00 ng/mL范围内呈良好的线性关系，回收率在96.9% ~ 99.6%之间，基质效应在98.9% ~ 104.6%之间。SB225002表现出可接受的短期、长期和冻融稳定性，所有其他项目均符合要求。利用该方法评估SB225002在小鼠体内的PK，揭示了快速吸收（tmax: 0.4±0.1 h, mean±SD）和代谢（t1/2: 3.4±2.6 h），并具有显著的个体间差异。结论：本研究成功建立并验证了UHPLC-MS/MS测定小鼠血浆中SB225002的方法，并首次报道了其在小鼠体内的药动学参数，为进一步的临床研究提供了可能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

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.