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目的建立灵敏、特异的LC-MS/MS方法测定小鼠血浆中紫杉醇浓度,并应用于小鼠静注水溶性多聚(L-谷氨酸)-丙氨酸-紫杉醇偶合物的药物动力学研究。方法用甲基叔丁基醚提取小鼠血浆样品,以多西紫杉醇为内标,在BetaBasicC18色谱柱上以流动相乙腈-水-甲酸(65∶35∶0.1,体积比)分离,流速为0.2ml/min;采用液相色谱-质谱-质谱联用仪,通过电喷雾离子化电离源,以选择反应监测方式进行正离子检测,用于定量分析的离子反应分别为m/z854.2→286.1(紫杉醇)和m/z808.3→527.2(多西紫杉醇)。结果测定紫杉醇的线性范围为0.5～1000ng/ml,相关系数r为0.9995,定量下限为0.5ng/ml,日内日间精密度分别小于11.52%和13.11%,准确度控制在87.05%～100.87%,提取回收率为85.04%～93.63%。结论该法快速、灵敏度高、专一性好,成功应用于小鼠静注10mg/kg水溶性多聚(L-谷氨酸)-丙氨酸-紫杉醇偶合物的药物动力学研究。
Objective To establish a sensitive and specific LC-MS / MS method for the determination of paclitaxel in mice plasma and to study the pharmacokinetics of water-soluble poly (L-glutamic acid) -alanine-paclitaxel conjugate in mice . Methods The plasma samples of mice were extracted with methyl tert-butyl ether. The docetaxel was separated on a BetaBasic C18 column with a mobile phase of acetonitrile-water-formic acid (65:35:0.1, by volume) at a flow rate of 0.2 ml / min. The positive ion was detected by electrospray ionization ionization ionization with liquid chromatography-mass spectrometry-mass spectrometry (MS-MS / MS), and the ion reaction for quantitative analysis was m / z854.2 → 286.1 (Paclitaxel) and m / z 808.3 → 527.2 (docetaxel). Results The linear range of paclitaxel was 0.5-1000 ng / ml, the correlation coefficient was 0.9995, the lower limit of quantitation was 0.5 ng / ml, the intra-day and inter-day precision were less than 11.52% and 13.11%, the accuracy was between 87.05% and 100.87% Extraction recovery was 85.04% ~ 93.63%. Conclusion The method is rapid, sensitive and specific and has been successfully applied to the pharmacokinetic study of intravenous injection of 10 mg / kg water-soluble poly (L-glutamic acid) -alanine-paclitaxel conjugate in mice.