Department of Quality Control, Yantai Central Blood Station, Yantai, Shandong Province, China.
Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong Province, China.
Biomed Chromatogr. 2020 Aug;34(8):e4862. doi: 10.1002/bmc.4862. Epub 2020 May 21.
A simple and sensitive ultra-high-performance liquid chromatography tandem mass spectrometric method was developed and validated for the determination of foretinib in rat plasma. The analyte and internal standard were extracted from the bio-samples with acetonitrile and then separated on an Acquity UPLC BEH C column (50 × 2.1 mm, 1.7 μm) using 0.1% formic acid aqueous and acetonitrile as mobile phase, at a flow rate of 0.4 ml/min. The mass detection was performed in positive selected reaction monitoring mode with precursor-to-product transitions at m/z 317.1 > 128.1 for foretinib and m/z 502.2 > 323.1 for internal standard. The assay was demonstrated to be linear in the concentration range of 0.5-1000 ng/ml, with correlation coefficient >0.999. The mean extraction recovery of foretinib from rat plasma was within the range of 84.55-88.09%, while the matrix effect was in the range of 88.56-99.21%. The intra- and inter-day precisions were <12.95% and the accuracy ranged from -7.55 to 8.57%. Foretinib was stable in rat plasma under the tested storage conditions. The validated assay was successfully applied to the pharmacokinetic study of foretinib in the rats. The results revealed that foretinib showed moderate elimination half-life, low clearance and dose-independent pharmacokinetic profiles inrats.
建立并验证了一种用于测定大鼠血浆中呋替尼的简单灵敏的超高效液相色谱-串联质谱法。分析物和内标物用乙腈从生物样品中提取，然后在 Acquity UPLC BEH C 柱（50×2.1mm，1.7μm）上分离，以 0.1%甲酸水溶液和乙腈为流动相，流速为 0.4ml/min。采用正离子选择反应监测模式进行质谱检测，母离子-子离子转换为 m/z 317.1>128.1 用于呋替尼，m/z 502.2>323.1 用于内标。该测定法在 0.5-1000ng/ml 的浓度范围内呈线性，相关系数>0.999。呋替尼从大鼠血浆中的平均提取回收率在 84.55-88.09%范围内，而基质效应在 88.56-99.21%范围内。日内和日间精密度均<12.95%，准确度在-7.55 至 8.57%范围内。呋替尼在测试的储存条件下在大鼠血浆中稳定。该验证后的测定法成功应用于大鼠中呋替尼的药代动力学研究。结果表明，呋替尼在大鼠中表现出中等消除半衰期、低清除率和剂量无关的药代动力学特征。
