Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)

Susan E. Abbatiello, D. R. Mani, Birgit Schilling, Brendan MacLean, Lisa J. Zimmerman, Xingdong Feng, Michael P. Cusack, Nell Sedransk, Steven C. Hall, Terri Addona, Simon Allen, Nathan G. Dodder, Mousumi Ghosh, Jason M. Held, Victoria Hedrick, H. Dorota Inerowicz, Angela Jackson, Hasmik Keshishian, Jong Won Kim, John S. Lyssand & 27 others C. Paige Riley, Paul Rudnick, Pawel Sadowski, Kent Shaddox, Derek Smith, Daniela Tomazela, Asa Wahlander, Sofia Waldemarson, Corbin A. Whitwell, Jinsam You, Shucha Zhang, Christopher R. Kinsinger, Mehdi Mesri, Henry Rodriguez, Christoph H. Borchers, Charles Buck, Susan J. Fisher, Bradford W. Gibson, Daniel Liebler, Michael MacCoss, Thomas A. Neubert, Amanda Paulovich, Fred Regnier, Steven J. Skates, Paul Tempst, Mu Wang, Steven A. Carr

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LCSID- MRM-MS platforms for routine use, with pass/fail criteria for system suitability performance measures defined as peak area coefficient of variation <0.15, peak width coefficient of variation <0.15, standard deviation of RT <0.15 min (9 s), and the RT drift <0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities.

Original languageEnglish
Pages (from-to)2623-2639
Number of pages17
JournalMolecular & cellular proteomics : MCP
Volume12
Issue number9
DOIs
StatePublished - Sep 2013

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Liquid chromatography
Liquid Chromatography
Monitoring
Isotopes
Dilution
Clinical laboratories
Assays
Biomedical Technology
Mass spectrometers
Early Diagnosis
Mass Spectrometry
Proteins
Software
Mass spectrometry
Data acquisition
Scheduling
Peptides
Research

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS). / Abbatiello, Susan E.; Mani, D. R.; Schilling, Birgit; MacLean, Brendan; Zimmerman, Lisa J.; Feng, Xingdong; Cusack, Michael P.; Sedransk, Nell; Hall, Steven C.; Addona, Terri; Allen, Simon; Dodder, Nathan G.; Ghosh, Mousumi; Held, Jason M.; Hedrick, Victoria; Inerowicz, H. Dorota; Jackson, Angela; Keshishian, Hasmik; Kim, Jong Won; Lyssand, John S.; Riley, C. Paige; Rudnick, Paul; Sadowski, Pawel; Shaddox, Kent; Smith, Derek; Tomazela, Daniela; Wahlander, Asa; Waldemarson, Sofia; Whitwell, Corbin A.; You, Jinsam; Zhang, Shucha; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Borchers, Christoph H.; Buck, Charles; Fisher, Susan J.; Gibson, Bradford W.; Liebler, Daniel; MacCoss, Michael; Neubert, Thomas A.; Paulovich, Amanda; Regnier, Fred; Skates, Steven J.; Tempst, Paul; Wang, Mu; Carr, Steven A.

In: Molecular & cellular proteomics : MCP, Vol. 12, No. 9, 09.2013, p. 2623-2639.

Research output: Contribution to journalArticle

Abbatiello, SE, Mani, DR, Schilling, B, MacLean, B, Zimmerman, LJ, Feng, X, Cusack, MP, Sedransk, N, Hall, SC, Addona, T, Allen, S, Dodder, NG, Ghosh, M, Held, JM, Hedrick, V, Inerowicz, HD, Jackson, A, Keshishian, H, Kim, JW, Lyssand, JS, Riley, CP, Rudnick, P, Sadowski, P, Shaddox, K, Smith, D, Tomazela, D, Wahlander, A, Waldemarson, S, Whitwell, CA, You, J, Zhang, S, Kinsinger, CR, Mesri, M, Rodriguez, H, Borchers, CH, Buck, C, Fisher, SJ, Gibson, BW, Liebler, D, MacCoss, M, Neubert, TA, Paulovich, A, Regnier, F, Skates, SJ, Tempst, P, Wang, M & Carr, SA 2013, 'Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)', Molecular & cellular proteomics : MCP, vol. 12, no. 9, pp. 2623-2639. https://doi.org/10.1074/mcp.M112.027078
Abbatiello, Susan E. ; Mani, D. R. ; Schilling, Birgit ; MacLean, Brendan ; Zimmerman, Lisa J. ; Feng, Xingdong ; Cusack, Michael P. ; Sedransk, Nell ; Hall, Steven C. ; Addona, Terri ; Allen, Simon ; Dodder, Nathan G. ; Ghosh, Mousumi ; Held, Jason M. ; Hedrick, Victoria ; Inerowicz, H. Dorota ; Jackson, Angela ; Keshishian, Hasmik ; Kim, Jong Won ; Lyssand, John S. ; Riley, C. Paige ; Rudnick, Paul ; Sadowski, Pawel ; Shaddox, Kent ; Smith, Derek ; Tomazela, Daniela ; Wahlander, Asa ; Waldemarson, Sofia ; Whitwell, Corbin A. ; You, Jinsam ; Zhang, Shucha ; Kinsinger, Christopher R. ; Mesri, Mehdi ; Rodriguez, Henry ; Borchers, Christoph H. ; Buck, Charles ; Fisher, Susan J. ; Gibson, Bradford W. ; Liebler, Daniel ; MacCoss, Michael ; Neubert, Thomas A. ; Paulovich, Amanda ; Regnier, Fred ; Skates, Steven J. ; Tempst, Paul ; Wang, Mu ; Carr, Steven A. / Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS). In: Molecular & cellular proteomics : MCP. 2013 ; Vol. 12, No. 9. pp. 2623-2639.
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T1 - Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)

AU - Abbatiello, Susan E.

AU - Mani, D. R.

AU - Schilling, Birgit

AU - MacLean, Brendan

AU - Zimmerman, Lisa J.

AU - Feng, Xingdong

AU - Cusack, Michael P.

AU - Sedransk, Nell

AU - Hall, Steven C.

AU - Addona, Terri

AU - Allen, Simon

AU - Dodder, Nathan G.

AU - Ghosh, Mousumi

AU - Held, Jason M.

AU - Hedrick, Victoria

AU - Inerowicz, H. Dorota

AU - Jackson, Angela

AU - Keshishian, Hasmik

AU - Kim, Jong Won

AU - Lyssand, John S.

AU - Riley, C. Paige

AU - Rudnick, Paul

AU - Sadowski, Pawel

AU - Shaddox, Kent

AU - Smith, Derek

AU - Tomazela, Daniela

AU - Wahlander, Asa

AU - Waldemarson, Sofia

AU - Whitwell, Corbin A.

AU - You, Jinsam

AU - Zhang, Shucha

AU - Kinsinger, Christopher R.

AU - Mesri, Mehdi

AU - Rodriguez, Henry

AU - Borchers, Christoph H.

AU - Buck, Charles

AU - Fisher, Susan J.

AU - Gibson, Bradford W.

AU - Liebler, Daniel

AU - MacCoss, Michael

AU - Neubert, Thomas A.

AU - Paulovich, Amanda

AU - Regnier, Fred

AU - Skates, Steven J.

AU - Tempst, Paul

AU - Wang, Mu

AU - Carr, Steven A.

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