A rapid analytical method for the quantification of paclitaxel in rat plasma and brain tissue by high-performance liquid chromatography and tandem mass spectrometry.
A rapid analytical method for the quantification of paclitaxel in rat plasma and brain tissue by high-performance liquid chromatography and tandem mass spectrometry.
复制标题
DOI：
10.1002/rcm.6671
复制
发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Pei Li;B. Albrecht;Xisheng Yan;Mei Gao;H. Weng;M. Bartlett
中科院分区：
文献类型：
--
作者：
Pei Li;B. Albrecht;Xisheng Yan;Mei Gao;H. Weng;M. Bartlett
理论依据Paclitazone是一种用于治疗几种类型癌症的抗肿瘤药物，最近有报道称其可导致人类认知功能受损和神经性疼痛。为了评估紫杉醇对中枢神经系统的影响，需要一种灵敏和准确的方法来定量从接受紫杉醇的啮齿动物中获得的血浆和脑组织中的紫杉醇浓度。方法生物样品经液-液萃取后，采用BDS Hypersil C8色谱柱，在等度条件下进行3.5min的反相液相色谱分离。使用多反应监测（MRM）与三重四极杆串联质谱仪在正电喷雾电离（ESI+）模式下工作定量紫杉醇。使用稳定同位素标记的紫杉醇类似物作为内标（IS）。结果经验证，该方法在基于100 μL血浆的0.5-100 ng/mL和基于33 mg脑组织匀浆的1.5-300 ng/g的动态范围内具有精密度和准确度。该方法适用于2 mg/kg静脉给药大鼠的样品。给药后4 h测量时，观察到血浆浓度为26.62 ± 8.93 ng/mL，脑浓度为11.08 ± 4.18 ng/g。结论该方法灵敏度高、特异性强、精密度好、准确度高，可用于大鼠血浆和脑组织匀浆中紫杉醇的定量分析。应用该方法研究样品提供了紫杉醇穿透血脑屏障的充分证据，允许进一步研究其对中枢神经系统的影响。
RATIONALE Paclitaxel, an antitumor agent for the treatment of several types of cancers, has recently been reported to cause impaired cognitive function and neuropathic pain in humans. To assess the effects of paclitaxel on the central nervous system, a sensitive and accurate method is required to quantify paclitaxel concentrations in plasma and brain tissue obtained from rodents receiving paclitaxel. METHODS The biological samples were prepared by liquid-liquid extraction and separated by a 3.5 min reversed-phase liquid chromatography (RPLC) method using a BDS Hypersil C8 column under isocratic conditions. Paclitaxel was quantified using multiple reaction monitoring (MRM) with a triple quadrupole tandem mass spectrometer working in the positive electrospray ionization (ESI+) mode. A stable isotope labeled analogue of paclitaxel was used as the internal standard (IS). RESULTS The method was validated to be precise and accurate within the dynamic range of 0.5-100 ng/mL based on 100 μL plasma and 1.5-300 ng/g based on 33 mg of brain tissue in homogenate. This method was applied to samples from 2 mg/kg intravenously dosed rats. The plasma concentrations were observed to be 26.62 ± 8.93 ng/mL and brain concentrations 11.08 ± 4.18 ng/g when measured 4 h post-dose. CONCLUSIONS This rapid LC/MS/MS method was validated to be sensitive, specific, precise and accurate for the quantification of paclitaxel in rat plasma and brain tissue homogenate. Application of the method to study samples provided sufficient proof of blood-brain barrier penetration of paclitaxel, allowing further investigation of its influence on the central nervous system.