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Title: Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer

Abstract

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 matrices. After development and selection of optimum MRM transition, 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 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 reference peptides. The sensitivity improvement observed with the IFT coupled to the triple quadrupole instrument is based on several unique features. First, ion accumulation in the 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 per unit time compared to a continuous mode of operation. Third, signal detectionmore » 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 up to 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 ~ 4 to ~ 8.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1009702
Report Number(s):
PNNL-SA-74498
40072; 400412000; TRN: US201107%%816
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Analytical Chemistry, 83(6):2162–2171
Additional Journal Information:
Journal Volume: 83; Journal Issue: 6
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ABUNDANCE; AMPLITUDES; CHARGE DENSITY; CHROMATOGRAPHY; DEAD TIME; DETECTION; EVALUATION; ION BEAMS; ION SOURCES; MASS SPECTROMETERS; MATRICES; MONITORING; PEPTIDES; QUADRUPOLES; SENSITIVITY; STRAINS; Environmental Molecular Sciences Laboratory

Citation Formats

Belov, Mikhail E, Prasad, Satendra, Prior, David C, Danielson, William F, Weitz, Karl K, Ibrahim, Yehia M, and Smith, Richard D. Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer. United States: N. p., 2011. Web. doi:10.1021/ac103006b.
Belov, Mikhail E, Prasad, Satendra, Prior, David C, Danielson, William F, Weitz, Karl K, Ibrahim, Yehia M, & Smith, Richard D. Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer. United States. https://doi.org/10.1021/ac103006b
Belov, Mikhail E, Prasad, Satendra, Prior, David C, Danielson, William F, Weitz, Karl K, Ibrahim, Yehia M, and Smith, Richard D. 2011. "Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer". United States. https://doi.org/10.1021/ac103006b.
@article{osti_1009702,
title = {Pulsed Multiple Reaction Monitoring Approach to Enhancing Sensitivity of a Tandem Quadrupole Mass Spectrometer},
author = {Belov, Mikhail E and Prasad, Satendra and Prior, David C and Danielson, William F and Weitz, Karl K and Ibrahim, Yehia M and Smith, Richard D},
abstractNote = {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 matrices. After development and selection of optimum MRM transition, 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 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 reference peptides. The sensitivity improvement observed with the IFT coupled to the triple quadrupole instrument is based on several unique features. First, ion accumulation in the 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 per unit time 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 up to 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 ~ 4 to ~ 8.},
doi = {10.1021/ac103006b},
url = {https://www.osti.gov/biblio/1009702}, journal = {Analytical Chemistry, 83(6):2162–2171},
number = 6,
volume = 83,
place = {United States},
year = {Wed Feb 23 00:00:00 EST 2011},
month = {Wed Feb 23 00:00:00 EST 2011}
}