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

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• 作者：Eugene Ciccimaro ; Asoka Ranasinghe ; Celia D鈥橝rienzo ; Carrie Xu ; Joelle Onorato ; Dieter M. Drexler ; Jonathan L. Josephs ; Michael Poss ; Timothy Olah
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：December 2, 2014
• 年：2014
• 卷：86
• 期：23
• 页码：11523-11527
• 全文大小：340K
• ISSN：1520-6882

文摘

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鈥檚 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鈥檚 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.