Strategy to improve the quantitative LC-MS analysis of molecular ions resistant to gas-phase collision induced dissociation: application to disulfide-rich cyclic peptides.
Due to observed collision induced dissociation (CID) fragmentation inefficiency, developing sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assays for CID resistant compounds is especially challenging. As an alternative to traditional LC-MS/MS, we present here a methodology that preserves the intact analyte ion for quantification by selectively filtering ions while reducing chemical noise. Utilizing a quadrupole-Orbitrap MS, the target ion is selectively isolated while interfering matrix components undergo MS/MS fragmentation by CID, allowing noise-free detection of the analyte's surviving molecular ion. In this manner, CID affords additional selectivity during high resolution accurate mass analysis by elimination of isobaric interferences, a fundamentally different concept than the traditional approach of monitoring a target analyte's unique fragment following CID. This survivor-selected ion monitoring (survivor-SIM) approach has allowed sensitive and specific detection of disulfide-rich cyclic peptides extracted from plasma.
Bristol-Myers Squibb , Princeton, New Jersey 08543, United States.
Eugene
E
Ciccimaro
Asoka
A
Ranasinghe
Celia
C
D'Arienzo
Carrie
C
Xu
Joelle
J
Onorato
Dieter M
DM
Drexler
Jonathan L
JL
Josephs
Michael
M
Poss
Timothy
T
Olah
D002853:Chromatography, Liquid; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D007477:Ions / Q000032:analysis / Q000737:chemistry; D010456:Peptides, Cyclic / Q000097:blood* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
D004220:Disulfides; D007477:Ions; D010456:Peptides, Cyclic