Quadrupole-Linear Ion Trap Tandem Mass Spectrometry System for Clinical Biomarker Analysis

Abstract

The accurate and efficient measurement of small molecule disease markers for clinical diagnosis is of great importance. In this study, a quadrupole-linear ion trap (Q-LIT) tandem mass spectrometer was designed and built in our laboratory. Target precursor ions were first selected in the quadrupole, and then injected, trapped, and fragmented simultaneously in the linear ion trap (LIT) to reduce the space charge effect, enrich the target product ions, and promote sensitivity. The targeted analytes were measured with selected reaction monitoring using a positive scan mode with electrospray ionization (ESI). Ions with a mass-to-charge ratio ( m / z ) ranging from 195 to 2022 were demonstrated. When scanning at 1218 amu·s −1 , unit resolution and an accuracy of higher than m/z 0.28 was obtained for m / z up to 2000. The dimensionless Mathieu parameter ( q ) value used in this study was 0.40 for collision-induced dissociation (CID), which was activated by resonance excitation. And an overall CID efficiency of 64% was achieved (activation time, 50 ms). Guanidinoacetic acid (GAA) and creatine (CRE) were used as model compounds for small molecule clinical biomarkers. The limits of quantification were 1.0 and 0.2 nmol·L −1 for GAA and CRE, respectively. A total of 77 actual samples were successfully analyzed by the home-built ESI-Q-LIT tandem mass spectrometry system. The developed method can reduce matrix interference, minimize space charge effects, and avoid the chromatographic separation of complex samples to simplify the pretreatment process. This novel Q-LIT system is expected to be a good candidate for the determination of biomarkers in clinical diagnosis and therapeutics.