HPLC检测人血浆中索拉非尼浓度

Determination of Sorafenib in Human Plasma by HPLC

关键词:  索拉非尼  高效液相色谱法  血浆浓度  治疗药物监测

Key words:  sorafenib  HPLC  plasma concentration  therapeutic drug monitoring

摘要:

目的 建立检测人血浆中索拉非尼浓度的高效液相色谱法。方法 采用ZORBAX XDB-C₁₈色谱柱(150 mm×4.6 mm，5 μm)；以乙腈-0.1%三氟乙酸-水(49∶20∶31)为流动相，流速为1.0 mL·min^-1，检测波长266 nm，柱温为35 ℃。以伊曲康唑为内标，血浆在碱性条件下经乙酸乙酯萃取后检测。结果 血浆索拉非尼浓度在0.05~10.00 mg·L^-1内线性关系良好(r=0.999 7)；低、中、高3个浓度(0.10，2.50，7.50 mg·L^-1)的日内精密度RSD分别为3.78％，2.31％和2.16％，日间精密度RSD分别为4.52％，3.46％和2.14％；方法回收率分别为(97.2±4.54)％，(100.8±2.51)％和(100.2±2.17)％；绝对回收率分别为(80.55±4.13)％，(81.42±2.91)％和(82.07±1.62)％。结论 该方法简便、准确，适用于索拉非尼临床治疗药物监测及其药动学研究。

Abstract:

OBJECTIVE To develop an HPLC method for the determination of sorafenib in human plasma. METHODS The analytical column was packed with ZORBAX XDB-C₁₈(150 mm×4.6 mm, 5 mm). A mixture of acetonitrile-0.1% trifluoroacetic acid-water(49∶20∶31) was used as the mobile phase with the flow rate of 1.0 mL·min^-1. The detection wavelength was set at 266 nm. The column temperature was set at 35 ℃. The plasma was extracted with ethyl acetate under basic conditions, and itraconazole was used as internal standard. RESULTS Excellent liner relationship was obtained in the range of 0.05-10.00 mg·L^-1(r=0.999 7). The intra-day RSDs were 3.78％, 2.31％and 2.16％, and inter-day RSDs were 4.52％, 3.46％ and 2.14％, respectively at three concentrations(0.1, 2.50, 7.50 mg·L^-1). The method recoveries were (97.2±4.54)%, (100.8±2.51)%, and (100.2±2.17)%, respectively. The absolute recoveries were (80.55±4.13)％, (81.42±2.91)％, (82.07±1.62)%, respectively. CONCLUSION The method is simple, accurate and sutiable for sorafenib cliniacl therapeutic drug monitoring and its pharmacokinetics study.