HPLC-MS/MS法测定大鼠血浆中长春花碱的浓度及药动学研究  

Concentration Determination and Pharmacokinetics of Vinblastine in Rat Plasma by HPLC-MS/MS

作　　者：翟学佳[1] 朱超然[1] 汪难喜 陈芬[1] 吕永宁[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院药剂科,武汉430022

出　　处：《中国药师》2016年第2期218-221,共4页China Pharmacist

基　　金：国家自然科学基金项目(编号:81473287)

摘　　要：目的:建立HPLC-MS/MS法测定大鼠血浆中长春花碱的浓度。方法:血浆样本加入适量内标,经乙腈直接沉淀蛋白后采用HPLC-MS/MS进行分析。色谱柱采用Ultimate C_(18)柱(150 mm×2.1 mm,5.0μm);流动相由乙腈-10 mmol·L^(-1)醋酸铵(含0.1%甲酸)(49:51)组成,柱温40℃;流速0.3 ml·min^(-1);采用电喷雾离子源(ESI),以多反应监测方式(MRM)进行定量分析。长春花碱和内标长春新碱在正离子模式下定量分析离子对分别为m/z 811.4→m/z 224.2和m/z 825.4→m/z 807.4。结果:长春花碱在0.475~950 ng·ml^(-1)内线性关系良好(r=0.997 1),最低定量限为0.475 ng·ml^(-1),提取回收率为89.15%~95.28%,日内、日间精密度RSD均不高于7.95%。药动学研究结果表明,长春花碱在大鼠体内的t_(1/2)为(5.86±2.37)h,AUC_(0-t)和AUC_(0-∞)分别为(68.45±14.51),(95.03±33.09)μg·L^(-1)·h。结论:该方法分析速度快、灵敏、准确,为临床进一步研究长春花碱和药物转运体提供了基础。长春花碱在大鼠体内的浓度较低,半衰期较长。Objective： To establish an HPLC-MS/MS method for the determination of vinblastine in rat plasma. Methods： Aceto- nitrile was used to precipitate protein in the samples after the addition of internal standard, and then the concentration was analyzed by HPLC/MS/MS. All the separations were carried out on an Ultimate Cls column （150 mm ×2.1 mm, 5.0 μm）. The mobile phase was composed of acetonitrile and 10 mmol · L-1 ammoniumacetate （ containing 0.1% formic acid） （49 ： 51 ） and was pumped at a flow rate of 0.3 ml · min - 1 under 40 ℃. The detection was performed with multiple reactions monitoring （MRM） using electrospray ionization （ESI）. The precursor/product ion transitions were monitored at m/z 811.4 →m/z 224.2 （positive ion mode） for vinblastine and m/z 825.4→m/z 807.4（ positive ion mode） for internal standard vincristine. Results： Good linearity of vinblastine was obtained with- in the range of 0. 457-950 ng · ml - 1 （r = 0.997 1 ）. The lower limit of quantification was 0. 457 ng - ml - i. The extraction recoveries were within the range of 89.15% -95.28%. The precision of intra- and inter-day was not more than 7.95%. T1/2 of vinblastine in rats was （5.86 ± 2.37） h, and AUC（0-t） and AUC（0-∞） was （68.45 ± 14.51 ） and （95.03± 33.09） μg · L-1 · h, respectively. Conclusion： The method is fast, sensitive and accurate, which provides research basis for the development of vinblastine and transporters research in medicine. The concentration of vinblastine in rats is low, and the half-life is long.

关 键 词：长春花碱 大鼠血浆 高效液相色谱-质谱联用法 药动学 

分 类 号：R969.1[医药卫生—药理学]