Quantitative determination of plasma cabozantinib concentration using HPLC-UV and its application to patients with renal cell carcinoma
Quantitative determination of plasma cabozantinib concentration using HPLC-UV and its application to patients with renal cell carcinoma
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DOI：
10.1002/bmc.5599
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发表时间：
2023-02-21
影响因子：
1.8
通讯作者：
Kanno, Hiroshi
中科院分区：
文献类型：
--
作者：
Maruyama, Shinichi;Kato, Masaru;Kanno, Hiroshi
卡博替尼是一种口服小分子酪氨酸激酶抑制剂，已成为晚期肾细胞癌（RCC）的标准治疗。然而，卡博替尼与高不良事件率相关。因此，个体化卡博替尼给药和监测可以帮助最大限度地提高其治疗效果并避免严重的不良事件。本研究开发并验证了使用HPLC-UV测定血浆中卡博替尼浓度的方法。将索拉非尼（一种内标物）添加到含有卡博替尼的血浆样品中。卡博替尼的校准曲线在25至4，000 ng/ml之间显示出良好的线性（R-2 = 1.00）。回收率在92.1%以上，日内和日间变异系数分别小于5.2%和6.8%。然后，我们应用该方法监测三名晚期RCC患者的卡博替尼血液水平，这些患者以20、40或60 mg/天的剂量服用卡博替尼。3级不良事件更可能发生在具有高剂量和血液水平的卡博替尼的患者中。由于其简单性，所开发的方法可用于综合医院，预计将有助于最大限度地提高药物疗效，并最大限度地减少许多接受卡博替尼治疗的RCC患者的严重不良事件。
Cabozantinib is an oral small-molecule tyrosine kinase inhibitor that has become a standard of care for advanced renal cell carcinoma (RCC). However, cabozantinib is associated with a high rate of adverse events. Therefore, individualised cabozantinib administration and monitoring could help maximise its therapeutic efficacy and avoid serious adverse events. This study developed and validated a method to determine cabozantinib concentration in plasma using HPLC-UV. Sorafenib, an internal standard, was added to the plasma sample containing cabozantinib. A calibration curve for cabozantinib showed good linearity (R-2 = 1.00), between 25 and 4,000 ng/ml. The recovery rate was above 92.1%, and the intra- and inter-day coefficients of variation were smaller than 5.2 and 6.8%, respectively. Then, we applied the method for monitoring cabozantinib blood levels in three patients with advanced RCC who were taking cabozantinib at a dose of 20, 40 or 60 mg/day. Grade 3 adverse events were more likely to occur in patients with high dosing and blood level of cabozantinib. Owing to its simplicity, the developed method can be used in general hospitals, and is expected to help maximise drug efficacy and minimise serious adverse events in many patients with RCC undergoing cabozantinib treatment.