Development and validation of a liquid chromatography with tandem mass spectrometry(LC-MS/MS) method for the determination of sunitinib in rabbit plasma  

液相色谱串联质谱法测定家兔血浆中舒尼替尼含量方法的建立与验证（英文）

作　　者：杨勇杰[1,2] 李佳林[1,2] 王欢[1,2] 覃小雅 卢晓静[1,2] 张兰馨[1,2] 张悦[1,2] 顾梦洁[1,2] 范田园[1,2] 

机构地区：[1]北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191 [2]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2015年第11期721-725,共5页中国药学（英文版）

摘　　要：A liquid chromatography with tandem mass spectrometry（LC-MS/MS） method has been developed and validated for the measurement of sunitinib in rabbit plasma. After protein precipitation with acetonitrile, samples were analyzed on a Zorbax Extend-C18 column（150 mm×4.6 mm, 5μm）. The mobile phase consisted of a mixture of acetonitrile and deionized water（containing 0.05% formic acid） at a ratio of 27：73（v/v）, and the flow rate was set at 0.8 mL /min. The column temperature was maintained at 30 oC. The LC eluate was detected by an electrospray ionization（ESI） source operated in the positive ion mode, and quantification was conducted using MRM of the transitions m/z 399.24→283.01 and m/z 415.19→178.00 for sunitinib and internal standard（IS, diltiazem hydrochloride）, respectively. The calibration curve was linear in the range of 2–600 ng/m L. The lower limit of quantification was 2 ng/mL. The method also exhibited satisfactory results in terms of sensitivity, specificity, accuracy（with relative error ranging from –4.0% to 1.1%）, precision（with intra- and inter-day relative standard deviations ranging from 2.8% to 9.5%）, matrix effect, recovery as well as stability. Taken together, our newly developed method was reliable to monitor sunitinib concentrations in rabbit plasma.本研究建立和验证了测定家兔血浆中舒尼替尼含量的液相色谱串联质谱法（LC-MS/MS）。含舒尼替尼的血浆样品经乙腈沉淀蛋白质后,用Zorbax Extended-C18色谱柱（150 mm×4.6 mm,5μm）分离,流动相为乙腈和0.05%甲酸水溶液（27：73,v/v）,流速为0.8 mL/min,色谱柱柱温30 oC。液相流出液使用电喷雾离子源（ESI,正离子模式）,质谱多反应监测模式检测,检测离子：舒尼替尼m/z 399.24→283.01;内标（盐酸地尔硫卓）：m/z 415.19→178.00。舒尼替尼在2–600 ng/mL范围内,线性关系良好,最低定量限为2 ng/m L。该方法的专属性、准确度（相对误差范围为–5.0%~1.1%）、精密度（相对标准偏差范围为2.8%~9.5%）、基质效应以及提取回收率均符合要求。结果显示,该方法为检测家兔血浆中舒尼替尼的含量提供了一种可靠的手段。

关 键 词：SUNITINIB LC-MS/MS Rabbit plasma 

分 类 号：R965[医药卫生—药理学]