College of Pharmacy, Hebei Medical University, Shijiazhuang 050000, China.
College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050000, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jul 15;1242:124217. doi: 10.1016/j.jchromb.2024.124217. Epub 2024 Jun 24.
Tyrosine kinase inhibitors (TKIs) are commonly used to treat various cancers. Literature suggests that the blood concentration of TKIs strongly correlates with their efficacy and adverse effects. Therefore, establishing a Therapeutic Drug Monitoring (TDM) methodology for TKI drugs is crucial to improving their clinical efficacy and minimizing the treatment-related adverse effects. However, quantifying their concentrations in the plasma using existing methods to avoid potential toxicity is challenging. Herein, seven TKIs, namely sorafenib tosylate, axitinib, erlotinib, cediranib, brivanib, linifanib, and golvatinib, were successfully analyzed in human plasma by following a quick, easy, cheap, effective, rugged, and safe (QuEChERS) pretreatment method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Briefly, biological samples were extracted using 1 mL of methanol, followed by the sequential addition of 250 mg of anhydrous magnesium sulfate and 25 mg of N-propylethylenediamine (PSA) for salinization and purification by adsorption, respectively. In this study, dovitinib was used as the internal standard. The seven TKIs were detected by the gradient elution method for 4 min in the positive ion electrospray mode. The mobile phase comprised methanol (phase A) and 0.1 % aqueous formic acid solution (phase B) on the Agilent Zorbax RRHD Stablebond Aq, (2.1 × 50 mm; 1.8 μm). Brivanib, linifanib, axitinib, sorafenib tosylate, and golvatinib exhibited good linearity in the range of 5-500 ng/mL, and erlotinib and cediranib exhibited good linearity in the range of 10-1000 ng/mL, with linear correlation coefficients (R) ≥ 0.99. The limits of detection and quantification were 0.60-0.18 ng/mL and 5-10 ng/mL, respectively. The intraday and interday accuracy values ranged from -6.12 % to 7.31 %, with a precision (RSD) of ≤ 10.57 %. The method was rapid, accurate, specific, simple, reproducible, and suitable for the quantitative determination of the seven TKIs in human plasma.
酪氨酸激酶抑制剂（TKIs）常用于治疗各种癌症。文献表明，TKI 的血药浓度与其疗效和不良反应密切相关。因此，建立 TKI 药物的治疗药物监测（TDM）方法对于提高其临床疗效和最大限度地减少治疗相关不良反应至关重要。然而，使用现有的方法来量化它们在血浆中的浓度以避免潜在的毒性具有挑战性。在此，通过快速、简单、廉价、有效、坚固和安全（QuEChERS）预处理方法结合超高效液相色谱-串联质谱（UPLC-MS/MS），成功分析了人血浆中的七种 TKI，即索拉非尼甲苯磺酸盐、阿西替尼、厄洛替尼、西地尼布、布立尼布、利伐替尼和戈拉替尼。简要地说，生物样本用 1 mL 甲醇提取，然后分别加入 250 mg 无水硫酸镁和 25 mg N-丙基乙二胺（PSA），用于盐化和吸附净化。在本研究中，多韦替尼被用作内标。七种 TKI 在正离子电喷雾模式下采用梯度洗脱法在 4 分钟内检测。流动相由甲醇（A 相）和 0.1%甲酸水溶液（B 相）组成，在 Agilent Zorbax RRHD Stablebond Aq 上（2.1×50mm；1.8μm）。布立尼布、利伐替尼、阿西替尼、索拉非尼甲苯磺酸盐和戈拉替尼在 5-500ng/mL 范围内具有良好的线性关系，厄洛替尼和西地尼布在 10-1000ng/mL 范围内具有良好的线性关系，线性相关系数（R）≥0.99。检测限和定量限分别为 0.60-0.18ng/mL 和 5-10ng/mL。日内和日间准确度值在-6.12%至 7.31%之间，精密度（RSD）≤10.57%。该方法快速、准确、特异、简单、重现性好，适用于人血浆中七种 TKI 的定量测定。
