PXD010535-1

PXD010535 is an original dataset announced via ProteomeXchange.

Title	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)
Description	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 LC-SID-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
HostingRepository	PanoramaPublic
AnnounceDate	2018-07-23
AnnouncementXML	Submission_2018-07-23_22:39:55.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Birgit Schilling
SpeciesList	scientific name: Bos taurus; NCBI TaxID: 9913;
ModificationList	Carboxymethyl
Instrument	TSQ Quantum; TSQ Vantage; 4000 QTRAP; QTRAP 5500; 6410 Triple Quadrupole LC/MS; 6460 Triple Quadrupole LC/MS; Xevo TQ-XS

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-23 08:29:15	ID requested
⏵ 1	2018-07-23 22:39:56	announced

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, 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). Mol Cell Proteomics, 12(9):2623-39(2013) [pubmed]

submitter keyword: mass spectrometry, quantification, selected reaction monitoring, system suitability, skyline

Susan E. Abbatiello
contact affiliation	The Broad Institute of MIT and Harvard
lab head
Birgit Schilling
contact affiliation	The Buck Institute for Research on Aging
contact email	bschilling@buckinstitute.org
dataset submitter

Panorama Public dataset URI