Corona Giuseppe, Casetta Bruno, Sandron Sara, Vaccher Emanuela, Toffoli Giuseppe
Division of Experimental and Clinical Pharmacology, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy.
Rapid Commun Mass Spectrom. 2008;22(4):519-25. doi: 10.1002/rcm.3390.
A simple and rapid method has been developed and validated for the quantitation of vincristine in human plasma by liquid chromatography/tandem mass spectrometry (LC/MS/MS) with atmospheric pressure chemical ionization using on-line solid-phase extraction. The method uses vinblastine as internal standard and the sample preparation is limited just to a plasma protein precipitation step. Further sample clean-up is carried out on-line through a perfusion column preceding an analytical phenyl LC column, the latter directly connected to the mass spectrometer. Quantitation is performed in multiple reaction monitoring mode using the transitions of m/z 825.3 --> 765.3 and 811.3 --> 751.3 for vincristine and vinblastine respectively. The assay was linear (r2 > or =0.99) in a concentration range from 0.1 to 500 ng/mL. Carry-over, measured on the experimental set-up, was less than 0.04%. Recovery for vincristine and the internal standard was within 90-95%. The intra-day and inter-day assay precision ranged from 1.2% to 6.8% RSD while mean percentage deviation from nominal value ranged from 0.01% to 6.1%. The proposed assay was found suitable for pharmacokinetics investigations and clinical therapeutic drug monitoring especially in pediatric cancer patients.
已开发并验证了一种简单快速的方法，用于通过液相色谱/串联质谱法（LC/MS/MS）结合大气压化学电离和在线固相萃取对人血浆中的长春新碱进行定量分析。该方法使用长春碱作为内标，样品制备仅局限于血浆蛋白沉淀步骤。进一步的样品净化通过在分析型苯基LC柱之前的灌注柱在线进行，该分析柱直接连接到质谱仪。定量分析在多反应监测模式下进行，长春新碱和长春碱分别使用m/z 825.3 --> 765.3和811.3 --> 751.3的跃迁。该测定法在0.1至500 ng/mL的浓度范围内呈线性（r2≥0.99）。在实验装置上测得的残留小于0.04%。长春新碱和内标的回收率在90%-95%之间。日内和日间测定精密度的相对标准偏差（RSD）范围为1.2%至6.8%，而与标称值的平均百分比偏差范围为0.01%至6.1%。结果表明，所提出的测定法适用于药代动力学研究和临床治疗药物监测，尤其是在儿科癌症患者中。
