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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 a HPLC-MS / MS method for the determination of vinblastine in rat plasma. Methods: The plasma samples were spiked with appropriate amount of internal standard, and the proteins were directly precipitated by acetonitrile and analyzed by HPLC-MS / MS. The column was equipped with an Ultimate C 18 column (150 mm × 2.1 mm, 5.0 μm). The mobile phase consisted of acetonitrile-10 mmol·L -1 ammonium acetate (0.1% formic acid) (49:51) Temperature 40 ℃, flow rate 0.3 ml · min -1. Electrospray ionization (ESI) was used for quantitative analysis by MRM (Multiple Reaction Monitoring). Vinblastine and the internal standard vincristine were quantitatively analyzed in positive ion mode m / z 811.4 → m / z 224.2 and m / z 825.4 → m / z 807.4, respectively. Results: The linear relationship of vinblastine in 0.475 ~ 950 ng · ml ~ (-1) was good (r = 0.997 1), the lowest limit of quantification was 0.475 ng · ml -1 and the recovery was 89.15% ~ 95.28 %, Intraday, day precision RSD no higher than 7.95%. The results of pharmacokinetics showed that the t 1/2 (1/2) of vinblastine in rats was (5.86 ± 2.37) h and the AUC 0-t and AUC 0 -∞ were 68.45 ± 14.51, (95.03 ± 33.09) μg · L -1 · h. Conclusion: The method is rapid, sensitive and accurate and provides the basis for further study of vinca alkaloids and drug transporters. Vinca alkaloids in rats lower concentrations, longer half-life.