摘要
目的:建立快速、灵敏的高效液相色谱串联质谱电喷雾法测定大鼠血清中尼洛替尼的浓度,并进行大鼠尼洛替尼胶囊的药动学研究。方法:以XDB C_(18)色谱柱分离,采用电喷雾离子源(ESI源);以维拉帕米为内标,血清样品经乙腈沉淀蛋白后,以甲醇(含0.1%甲酸):水(含0.1%甲酸)=50:50为流动相,流速为0.35 ml·min^(-1)。以多反应监测(MRM)方式进行正离子检测,监测离子对分别是m/z 530.2→289.1(尼洛替尼)和内标m/z 455.3→165(维拉帕米)。结果:血清中尼洛替尼的线性范围在5～2000 ng·ml^(-1)良好。尼洛替尼在大鼠体内的主要药动学参数.AUC_(0-24)、C_(max)、t_(max)、t_(1/2z)、CLz/F分别为(10 055.37±1 405.49)ng·h·ml^(-1)、(1273.56±329.49)ng·ml^(-1)、(6.17±3.37)h、(1.86±1.04)h、(2.01±0.27)L·h^(-1)·kg^(-1)。结论:本试验建立的分析方法专属性好,灵敏度高,准确快捷,适用于尼洛替尼大鼠血清生物样品的快速检测。
Objective： To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometric （LC-MS/MS） method for the determination of nilotinib in rat serum and study the pharmacokinetics of nilotinib capsules in rats. Method： Serum samples were separated using verapamil as the internal standard on a XDB Cls column after protein precipitation with acetonitrile. The mobile phase consisted of methanol with 0.1% formic acid-water with 0.1% formic acid （50： 50） at a flow rate of 0.35 ml .min^-1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in the positive ion mode. Multiple Reaction Monitoring （MRM） using the precursor / product ion combinations was m/z 530.2→289.1 for nilotinib and m/z 455.3→165 for the internal standard verapamil, respectively. Result： The linear concentration range of the calibration curve was 5 - 2000 ng · ml^-1 for nilotinib. The main parameters of AUC0-24, Cmax, tmax ,t1/2z and CLz/F was （ 10 055.37 ± 1 405.49） ng·h·ml^- 1, （ 1 273.56 ± 329.49） ng · ml^ - 1, （6.17 ± 3.37） h, （ 1.86 ± 1.04） h and （2.01 ± 0.27 ） L · h ^- 1· kg^- 1, respectively. Conclusion： The method has been proved to be sensitive, simple, rapid and suitable for the determination of nilotinib serum concentrations in rats.
出处
《中国药师》
CAS
2012年第2期151-155,共5页
China Pharmacist
基金
"十一五"国家科技重大专项(编号:2009ZX09502-021)
上海交通大学医学院科研基金(编号:JYY0909)
