Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry
Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry
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DOI：
10.1016/j.chroma.2012.12.026
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发表时间：
2013-02-01
影响因子：
4.1
通讯作者：
Jiang, Ji
中科院分区：
文献类型：
--
作者：
Yang, Fen;Wang, Hongyun;Jiang, Ji
硫酸长春新碱脂质体是将传统抗癌药物硫酸长春新碱包裹在磷脂/胆固醇脂质体的水溶性核心中的脂质体制剂，是一种靶向载体，可增强药物的恶性肿瘤靶向、暴露和抗癌活性。为了评价和比较非脂质体和脂质体包封VCR的药代动力学以及与毒性和疗效行为相关的药效学关系，必须有一种分离游离和脂质体形式药物的可靠方法。本文中，我们开发并验证了硫酸长春新碱脂质体注射液（VSLI）静脉给药后人血浆中游离长春新碱（F-VCR）和总长春新碱（T-VCR）的定量方法。这些方法包括固相萃取（SPE）分离F-VCR和液液萃取（LLE）从脂质体形式中完全释放VCR，然后采用超高效液相色谱串联质谱法（UHPLC-MS/MS）。在三重四极杆串联质谱仪上以多反应监测（MRM）模式使用正离子电喷雾电离（ESI）进行检测。分别在0.2-50 ng/mL（F-VCR）和0.5-400 ng/mL（T-VCR）浓度范围内验证了方法。日间和日内精密度（RSD%）为
Vincristine sulfate liposome is a liposomal formulation of vincristine sulfate, a traditional anticancer drug, encapsulated in the aqueous core of phospholipid/cholesterol liposomes, which are kinds of targeted carriers to enhance malignancy targeting, exposure and anticancer activity of the drug. To evaluate and compare the pharmacokinetics of nonliposomal and liposome-encapsulated VCR and pharmacodynamic relationships associated with the toxicity and the efficacy behavior, it is essential to have a reliable method of separating the free and liposomal forms of the drug. In this paper, we have developed and validated methods to quantify the free vincristine (F-VCR) and total vincristine (T-VCR) in human plasma after intravenous administration of vincristine sulfate liposome injection (VSLI). The methods involve solid-phase extraction (SPE) for separating the F-VCR and liquid-liquid extraction (LLE) for releasing the VCR totally from the liposomal forms followed by an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The methods were validated over the concentration range of 0.2-50 ng/mL for F-VCR and 0.5-400 ng/mL for T-VCR, respectively. Inter- and intra-day precision (RSD%) were