LC-MS/MS法测定犬血中长春瑞滨浓度及药动学特征

Determination of vinorelbine in Beagle dog's plasma by LC-MS/MS and its pharmacokinetic profile

目的建立LC-MS/MS法测定犬血浆中长春瑞滨的浓度并进行药动学研究。方法将犬血浆经甲醇蛋白沉淀处理后稀释进样。色谱柱为Agilent SB-C_(18)柱;流动相为甲醇-2 mmol·L^(-1)醋酸铵水溶液-甲酸(75:25:0.1);流速为0.3 mL·min^(-1)。采用电喷雾离子源,正离子方式多反应监测(MRM)扫描分析。检测离子通道分别为m/z 779.5→658.5(长春瑞滨)和m/z 309.1→163.2(华法林)。结果长春瑞滨的线性范围为1~100μg·L^(-1)(R^2>0.99),定量限为1μg·L^(-1)。批内和批间精密度均<5.87%,高、中、低浓度的方法回收率为96.55%~102.2%。结论本方法操作简捷,灵敏度高,专属性好,适用于长春瑞滨的犬体内药动学研究。

AIM To establish a high performance liquid chromatography- tandem mass spectrometry method(LCMS/MS) method for the determination of vinorelbine in Beagle dog's plasma and study its pharmacokinetics.METHODS Protein precipitation process was used to extract vinorelbine from Beagle dog's plasma.Plasma samples were separated by HPLC on an Agilent SB-C_(18) column using a mobile phase consisting of methanol-2 mmol·L^(-1) ammonium acetate-formic acid(75:25:0.1) and the flow rate was set at 0.30 mL· min^(-1).The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring(MRM) mode using the respective[M + H]~ + ions m/z779.5→658.5 for vinorelbine and m/z 309.1→163.2 for warfarin(internal standard,IS).RESULTS The calibration curve was linear over the range of 1- 100 μg·L^(-1)(R^2 >0.99) with a limit of quantitation(LOQ) of 1 μg· L^(-1).The intra- and inter-day precision(relative standard deviation,RSD) values were below 5.87%and the mean accuracy was from 96.55%to 102.2%at three quality control levels.Vinorelbine was stable during stability studies.CONCLUSION The method is proved to be simple,convenient,accurate and sensitive,and suitable for the determination of vinorelbine in Beagle dog's plasma.