HPLC测定人血浆中舒尼替尼浓度及其血浆蛋白结合率

Determination of Sunitinib and Its Plasma Protein Binding Rate in Human Plasma by HPLC

关键词:  舒尼替尼  血浆蛋白结合率  平衡透析法  超滤法  高效液相色谱法

Key words:  sunitinib  binding rate of plasma protein  equilibrium dialysis  ultrafiltration  HPLC

摘要:

目的 采用HPLC测定人血浆中舒尼替尼浓度，并结合平衡透析法和超滤法测定舒尼替尼血浆蛋白结合率。方法 采用Waters XBridge^TM C₁₈色谱柱（4.6 mm×250 mm，5 μm），流动相为甲醇-0.02 mol·L^-1磷酸二氢钠（70：30），流速1.0 mL·min^-1，检测波长310 nm。结果 舒尼替尼在0.057 5~34.5 μg·mL^-1内线性关系良好，定量下限为0.057 5 μg·mL^-1；舒尼替尼在低、中、高3个浓度下平衡透析法测得的血浆蛋白结合率为（84.1±2.1）%，（81.0±1.8）%，（80.6±1.6）%，超滤法蛋白结合率分别为（80.8±1.7）%，（84.2±2.0）%，（82.6±2.2）%，2种方法结果比较接近。结论 本方法简单、快速、灵敏，能满足分析要求。舒尼替尼与人血浆蛋白有较高的结合率，且蛋白结合率与浓度无关。

Abstract:

OBJECTIVE To establish HPLC method combined with equilibrium dialysis or ultrafiltration for the determination of sunitinib and its plasma protein binding rate in human plasma. METHODS The HPLC analysis of sunitinib was achieved on Waters XBridge^TM C₁₈ (4.6 mm×250 mm, 5 µm) with a mobile phase composing of methanol-0.02 mol·L^-1 sodium dihydrogen phosphate (70:30) at a flow rate of 1.0 mL·min^-1, and the detection wavelength was 310 nm. RESULTS The calibration curve for plasma sunitinib was linear in the range of 0.057 5-34.5 μg·mL^-1, and the lower limit of quantification was 0.057 5 μg·mL^-1. At three different concentrations, the plasma protein binding rates were (84.1±2.1)%, (81.0±1.8)%, (80.6±1.6)% by equilibrium dialysis, respectively, and were (80.8±1.7)%, (84.2±2.0)%, (82.6±2.2)% accordingly by ultrafiltration. Both results were quite similar. CONCLUSION The HPLC method is simple, rapid, sensitive, and can effectively meet the needs of further analysis. And sunitinib has high plasma protein binding rate, which is independent of its plasma concentration.