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Herein we describe a new method, targeted enhanced multiply charged scans (tEMC), for the quantification of therapeutic peptides in tandem mass spectrometry on the linear ion trap mass spectrometer. Therapeutic peptides with chain lengths between eight and 39 amino acid residues and charge states from 2+ to 6+ were used to evaluate and illustrate the method which relies on the ability to separate ions trapped in a linear ion trap according to their charges. In particular, interference from singly charged ions on multiply charged ions can be effectively minimized. The method requires optimization of relatively few parameters, the most important of which being the exit lens barrier (EXB) voltage, thereby offering substantial time saving in a high-throughput quantification environment that currently relies on selected reaction monitoring.

Performance and Attributes of Liquid Chromatography–Mass Spectrometry with Targeted Charge Separation in Quantitative Analysis of Therapeutic Peptides