Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer
Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer
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DOI：
10.1021/ac103006b
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发表时间：
2011-03-15
影响因子：
7.4
通讯作者：
Smith, Richard D.
中科院分区：
文献类型：
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作者：
Belov, Mikhail E.;Prasad, Satendra;Smith, Richard D.
以多反应监测（MRM）模式操作的液相色谱（LC）-三重四极杆质谱仪越来越多地用于定量分析高度复杂的生化基质中的低丰度分析物。在开发和选择最佳MRM转换后，灵敏度和数据质量限制在很大程度上与样品或基质成分的质谱峰干扰以及到达检测器的离子数量较少时的统计限制有关。在这里，我们报告了一种新的方法来提高MRM的灵敏度，通过使用离子漏斗阱（IFT）的离子源转换成脉冲离子束的离子的连续流。用加标几种模型肽的希瓦氏菌菌株MR-1的胰蛋白酶消化物进行脉冲MRM方法的评价。IFT耦合到三重四极杆仪器观察到的灵敏度提高是基于几个独特的功能。首先，离子积累射频（rf）离子阱有利于改善液滴去溶剂化，这表现在检测器处的背景离子噪声降低。第二，由于与连续操作模式相比离子电荷密度的数量级增加，给定转变的信号幅度增强。第三，获得了全占空比下的信号检测，因为阱的使用消除了转换之间的死区时间，这对于连续的离子流是不可避免的。与传统方法相比，脉冲MRM信号显示出5倍增强的峰值幅度和2-3倍减少的化学背景，导致检测限（LOD）的改善，由一个类似的因素-4-8。
Liquid chromatography (LC)-triple quadrupole mass spectrometers operating in a multiple reaction monitoring (MRM) mode are increasingly used for quantitative analysis of low-abundance analytes in highly complex biochemical matrixes. After development and selection of optimum MRM transitions, sensitivity and data quality limitations are largely related to mass spectral peak interferences from sample or matrix constituents and statistical limitations at low number of ions reaching the detector. Herein, we report on a new approach to enhancing MRM sensitivity by converting the continuous stream of ions from the ion source into a pulsed ion beam through the use of an ion funnel trap (IFT). Evaluation of the pulsed MRM approach was performed with a tryptic digest of Shewanella oneidensis strain MR-1 spiked with several model peptides. The sensitivity improvement observed with the IFT coupled in to the triple quadrupole instrument is based on several unique features. First, ion accumulation radio frequency (rf) ion trap facilitates improved droplet desolvation, which is manifested in the reduced background ion noise at the detector. Second, signal amplitude for a given transition is enhanced because of an order-of-magnitude increase in the ion charge density compared to a continuous mode of operation. Third, signal detection at the full duty cycle is obtained, as the trap use eliminates dead times between transitions, which are inevitable with continuous ion streams. In comparison with the conventional approach, the pulsed MRM signals showed 5-fold enhanced peak amplitude and 2-3-fold reduced chemical background, resulting in an improvement in the limit of detection (LOD) by a factor of similar to-4-8.