通过MS / MSALL技术与混合四极杆飞行时间质谱同时定量分析大鼠中的聚乙二醇（PEG），聚乙二醇化的紫杉醇和紫杉醇。,Journal of Pharmaceutical and Biomedical Analysis

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通过MS / MSALL技术与混合四极杆飞行时间质谱同时定量分析大鼠中的聚乙二醇（PEG），聚乙二醇化的紫杉醇和紫杉醇。
Journal of Pharmaceutical and Biomedical Analysis ( IF 3.1 ) Pub Date : 2017-07-09 , DOI: 10.1016/j.jpba.2017.06.053
Heping Sun ₁ , Qi Zhang ₁ , Zhi Zhang ₁ , Jin Tong ₁ , Dafeng Chu ₂ , Jingkai Gu ₃

Affiliation

聚乙二醇化实际上是包括小分子，肽和蛋白质在内的药物最重要的修饰之一，已被证明可大大改善聚乙二醇化药物的理化性质和药代动力学行为。但是，由于分子量的多分散性导致PEG的多母体离子分布，因此通过各种分析方法甚至质谱定量分析PEG和PEG化药物是当前的挑战。在这里，我们使用电喷雾电离（ESI）源耦合高分辨率四极杆飞行时间（Q-TOF）质谱技术开发了一种可靠的MS / MSALL技术，用于定量PEG2K-紫杉醇（PEG-PTX）及其两种代谢物，PEG和紫杉醇（PTX）。分析是在带有乙腈和0的300SB-C18色谱柱上进行的。1％甲酸作为流动相。通过在少量血浆（50μL）中进行蛋白质沉淀即可简单地制备样品。校准曲线在PEG和PEG-PTX的50.0-4000ng / mL范围内，对于PTX在1.0-1000ng / mL的范围内呈线性关系。PEG的日内和日间精度分别为3.2-6.9％和3.1-6.9％，PEG-PTX为4.1-7.8％和4.0-9.9％，PTX为3.3-4.8％和3.1-6.9％。回收率大于90％，基质效应低。之后，新开发的方法成功地用于支持单次静脉注射PEG-PTX（51.7mg / kg）后在六只大鼠中进行临床前药代动力学研究。PEG的日内和日间精度分别为3.2-6.9％和3.1-6.9％，PEG-PTX为4.1-7.8％和4.0-9.9％，PTX为3.3-4.8％和3.1-6.9％。回收率大于90％，基质效应低。之后，新开发的方法成功地用于支持单次静脉注射PEG-PTX（51.7mg / kg）后在六只大鼠中进行临床前药代动力学研究。PEG的日内和日间精度分别为3.2-6.9％和3.1-6.9％，PEG-PTX为4.1-7.8％和4.0-9.9％，PTX为3.3-4.8％和3.1-6.9％。回收率大于90％，基质效应低。之后，新开发的方法成功地用于支持单次静脉注射PEG-PTX（51.7mg / kg）后在六只大鼠中进行临床前药代动力学研究。

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Simultaneous quantitative analysis of polyethylene glycol (PEG), PEGylated paclitaxel and paclitaxel in rats by MS/MSALL technique with hybrid quadrupole time-of-flight mass spectrometry.

PEGylation is practically one of most important modifications of drugs including small molecules, peptides and proteins, which has been proven to dramatically improve physicochemical properties and pharmacokinetic behavior of the PEGylated drugs. However, it is a challenge currently to quantitatively analyze PEG and PEGylated drugs by various analytical methods, even mass spectrometry because of multiple parent ion distribution of PEG caused by its polydispersity of molecular weight. Here we developed a robust method with MS/MSALL technique using electrospray ionization (ESI) source coupled high resolution Quadrupole Time-of-Flight (Q-TOF) mass spectrometry for the quantification of PEG2K-Paclitaxel (PEG-PTX) and its two metabolites, PEG and Paclitaxel (PTX). The analysis was performed on a 300SB-C18 column with acetonitrile and 0.1% formic acid as the mobile phase. Samples were simply prepared by protein precipitation in a small quantity of plasma (50μL). Calibration curve was linear within the range of 50.0-4000ng/mL for PEG and PEG-PTX and 1.0-1000ng/mL for PTX. The intra- and inter-day precisions were 3.2-6.9% and 3.1-6.9% for PEG, 4.1-7.8% and 4.0-9.9% for PEG-PTX, and 3.3-4.8% and 3.1-6.9% for PTX, respectively. The recoveries were greater than 90% with low matrix effects. Afterwards, the newly developed method was successfully applied to support a preclinical pharmacokinetic study in six rats after single intravenous injection of PEG-PTX (51.7mg/kg).

更新日期：2017-06-23

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