Determination of paclitaxel in mouse plasma and brain tissue by liquid chromatography-mass spectrometry
Determination of paclitaxel in mouse plasma and brain tissue by liquid chromatography-mass spectrometry
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DOI：
10.1016/j.jchromb.2003.08.049
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发表时间：
2003-12-05
影响因子：
3
通讯作者：
Gallo, JM
中科院分区：
文献类型：
--
作者：
Guo, P;Ma, JG;Gallo, JM
紫杉醇是从红豆杉树皮中提取的抗癌药物，广泛用于实体瘤的化疗，包括非小细胞肺癌和卵巢癌。大多数测量血浆中紫杉醇的测定方法需要大量样品（0.4-1 ml）才能达到必要的灵敏度，并且在只有小样品量时不适合。为了规避后一个限制，我们开发了一种灵敏的液相色谱-质谱 (LC-MS) 方法，用于基于小样本量（50 μl 血浆）测定血浆中的紫杉醇。采用固相萃取程序，使洗脱液能够直接注射到反相色谱 HPLC 系统上，使用正电喷雾电离，然后进行质谱检测。血浆和脑组织中紫杉醇的提取回收率分别为 98% 和 83%。流动相由 0.1% 甲酸中的 50% 乙腈组成，以 0.2 ml/min 的速度泵送，紫杉醇的保留时间为 6.2 分钟，三尖杉宁碱（内标）的保留时间为 5.4 分钟。该方法已在紫杉醇血浆浓度为 0.036 至 9.9 mug/ml 以及脑匀浆中紫杉醇浓度为 0.054 至 1.96 mug/ml 时得到验证。已经开发出一种灵敏且特异的紫杉醇测定方法，其优点是使用小样本量，并且单个提取步骤无需溶剂蒸发。 (C) 2003 Elsevier B.V. 保留所有权利。
Paclitaxel is an anticancer agent extracted from the bark of the yew tree and is widely used in chemotherapy for solid tumors, including non-small cell lung cancer and ovarian carcinoma. Most assays to measure paclitaxel in plasma require a large amount of sample (0.4-1 ml) to achieve the necessary sensitivity, and are not suitable when only small sample sizes are available. To circumvent this latter limitation, we developed a sensitive liquid chromatography-mass spectrometry (LC-MS) method for the determination of paclitaxel in plasma based on the use of small sample volumes (50 mul plasma). A solid phase extraction procedure was employed that enabled the eluent to be directly injected onto a reversed phase chromatographic HPLC system using positive electrospray ionization followed by mass spectrometric detection. The extraction recoveries of paclitaxel were 98 and 83% from plasma and brain tissues, respectively. The mobile phase consisted of 50% acetonitrile in 0.1% formic acid that was pumped at 0.2 ml/min to yield a retention time for paclitaxel of 6.2 and 5.4 min for cephalomannine, the internal standard. The method has been validated at paclitaxel plasma concentrations from 0.036 to 9.9 mug/ml, and from 0.054 to 1.96 mug/ml in brain homogenates. A sensitive and specific assay for paclitaxel has been developed that has the advantages of using small sample sizes, and a single extraction step without solvent evaporation. (C) 2003 Elsevier B.V. All rights reserved.