Strategy to Improve the Quantitative LC-MS Analysis of Molecular Ions Resistant to Gas-Phase Collision Induced Dissociation: Application to Disulfide-Rich Cyclic Peptides

被引：19

作者：

Ciccimaro, Eugene ^{[1
]}

Ranasinghe, Asoka ^{[1
]}

D'Arienzo, Celia ^{[1
]}

Xu, Carrie ^{[1
]}

Onorato, Joelle ^{[1
]}

Drexler, Dieter M. ^{[1
]}

Josephs, Jonathan L. ^{[2
]}

Poss, Michael ^{[1
]}

Olah, Timothy ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Princeton, NJ 08543 USA

[2] ThermoFisher Sci, San Jose, CA 95134 USA

来源：

ANALYTICAL CHEMISTRY | 2014年 / 86卷 / 23期

关键词：

CYSTINE KNOT MOTIF; MASS-SPECTROMETRY; TRIPLE QUADRUPOLE; DRUG DESIGN; QUANTIFICATION; BIOANALYSIS; ACTIVATION; PROTEINS; SPECTRA; TRAP;

D O I：

10.1021/ac502678y

中图分类号：

O65 [分析化学];

学科分类号：

070302 [分析化学];

摘要：

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.

引用

页码：11523 / 11527

页数：5

共 21 条

[1]

Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds [J].