Keil C, Götze L, Olbert P, Hofmann R, Nockher W A, Hegele A
Klinik für Urologie und Kinderurologie, Universitätsklinikum Gießen und Marburg, Standort Marburg, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland,
Urologe A. 2015 Jun;54(6):811-8. doi: 10.1007/s00120-014-3711-1.
Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS).
A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry.
The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals.
Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.
几种酪氨酸激酶抑制剂(TKI)用于治疗转移性肾细胞癌(mRCC)。本文介绍了一项使用液相色谱串联质谱法(LC-MS/MS)测量舒尼替尼、索拉非尼和帕唑帕尼血浆水平的可行性研究。
共纳入23例接受舒尼替尼(n = 16)、索拉非尼(n = 3)和帕唑帕尼(n = 4)治疗的mRCC患者。通过液相色谱分析分离血浆样本(100 μl),并通过串联质谱法测定TKI的血浆水平。
舒尼替尼、索拉非尼和帕唑帕尼的血浆水平可测量且结果可重复。血浆样本在4°C储存1周期间,未发现初始浓度有显著下降。检测到的最高血浆水平分别为舒尼替尼99 ng/ml、索拉非尼9.8 μg/ml和帕唑帕尼63 μg/ml。我们可以显示出TKI血浆水平根据TKI剂量变化或在无治疗间隔期间的变异性。
使用LC-MS/MS测量TKI血浆水平是可行的。必须进行进一步的临床研究,以检查不良事件发生率或治疗反应是否存在任何阈值水平。