Toxicity induced by crizotinib, a small-molecule tyrosine kinase inhibitor, is a significant clinical issue during treatment. A tissue distribution study is required to explore the organs affected by this molecule. In this study, a simple liquid chromatography tandem mass spectrometry method was developed and validated for the determination of crizotinib in various mouse tissues. Mouse tissue homogenates were processed by protein precipitation with methanol, and apatinib was chosen as the internal standard. The analytes were separated on a Phenomenex Kinetex C₁₈ (50 mm × 2.1 mm, 2.6 μm) column with gradient elution using methanol and 0.3% formic acid water solution. Tandem mass spectrometric detection was conducted using multiple reaction monitoring via an electrospray ionization source in the positive mode. The monitored ion transitions were m/z 450.1 ⟶ 260.2 for crizotinib and m/z 398.2 ⟶ 212.0 for apatinib. The problem of the severe carryover effect was successfully resolved. The method was validated and applied to a tissue distribution study of crizotinib in mice, which was reported for the first time. The results of the study showed that the main target organs of crizotinib were the lung, liver, and spleen, and a high concentration of crizotinib was found in the gastrointestinal tract. This study offers a reliable method for quantifying crizotinib and provides a basis for further research on crizotinib toxicity.

中文翻译：

---

LC-MS / MS法测定小鼠组织中的克唑替尼及其在组织分布研究中的应用

克唑替尼（一种小分子酪氨酸激酶抑制剂）引起的毒性是治疗期间的重要临床问题。需要进行组织分布研究以探索受该分子影响的器官。在这项研究中，开发了一种简单的液相色谱串联质谱法，并已验证了该法可用于测定各种小鼠组织中的克唑替尼。小鼠组织匀浆通过用甲醇进行蛋白质沉淀处理，并选择阿帕替尼作为​​内标。将分析物在Phenomenex Kinetex下分离₁₈英寸（50毫米×2.1毫米，2.6  μm）使用甲醇和0.3％甲酸水溶液进行梯度洗脱的色谱柱。串联质谱检测是通过正离子模式下通过电喷雾电离源使用多反应监测进行的。克唑替尼和m / z的受监测离子跃迁为m / z 450.1⟶260.2阿帕替尼398.2-212.0。严重结转效应的问题已成功解决。该方法经过验证，并应用于克唑替尼在小鼠中的组织分布研究，这是首次报道。研究结果表明，克唑替尼的主要靶器官是肺，肝和脾，在胃肠道中发现了高浓度的克唑替尼。该研究提供了定量克唑替尼的可靠方法，并为克唑替尼毒性的进一步研究提供了基础。