Two-Dimensional Tandem Mass Spectrometry in a Single Scan on a Linear Quadrupole Ion Trap

Abstract

A two-dimensional tandem mass spectrometry (2D MS/MS) scan has been developed for the linear quadrupole ion trap. Precursor ions are mass-selectively excited using a nonlinear ac frequency sweep at constant rf voltage, while simultaneously, all product ions of the excited precursor ions are ejected from the ion trap using a broad-band waveform. The fragmentation time of the precursor ions correlates with the precursor m/z value (the first mass dimension) and also with the ejection time of the product ions, allowing the correlation between precursor and product ions. Additionally, the second mass dimension (product ions’ m/z values) is recovered through fast Fourier transform of each mass spectral peak, revealing either intentionally introduced “frequency tags” or the product ion micropacket frequencies, both of which can be converted to product ion m/z through the classical Mathieu parameters, thereby revealing a product ion mass spectrum for every precursor ion without prior isolation. We demonstrate the utility of this method for analyzing a broad range of structurally related precursor ions, including chemical warfare agent simulants, fentanyls and other opioids, amphetamines, cathinones, antihistamines, and tetracyclic antidepressants.

2D MS/MS Spectra Recorded in the Time Domain Using Repetitive Frequency Sweeps in Linear Quadrupole Ion Traps

“…Previous 2D MS/MS experiments using a linear quadrupole ion trap were performed using the same fragmentation waveform as done in this study but by ejecting the product ions using a sum of sines broadband waveform . The product ion information was determined from iterative fast Fourier transforms across the mass spectrum.…”

“…More recent FT-ICR-based improvements in 2D-MS/MS include coupling radius dependent fragmentation methods, phase correction of the signal output, and rf pulse sequence optimization . Recently, our group demonstrated the experimental implementation of two-dimensional tandem mass spectrometry (2D MS/MS) in a single scan of a linear quadrupole ion trap. , The FT-ICR experiment provides high resolution on a wide range of precursor ions; however, this method requires ultrahigh vacuum instrumentation, a superconducting magnet, and lengthy acquisition times. , By contrast, the quadrupole ion trap method has modest vacuum requirements and short acquisition times, albeit with reduced mass range and resolution; as such it should be best suited to implementation in the form of a miniature mass spectrometer for on-site analysis. , …”

“…Most commercial ion trap detection circuits are too slow to detect ion micromotion, so a second method, frequency tagging, was implemented (Figure b) . In this method, each secular frequency was modulated by a unique low frequency beat.…”

Phase Correction for Absorption Mode Two-Dimensional Mass Spectrometry

“…Two-dimensional mass spectrometry (2D MS) is a tandem mass spectrometry method that relies on manipulating ion motions to correlate precursor and fragment ion signals [ 1 , 2 , 3 ]. Various 2D MS methods have been developed for quadrupolar ion traps, linear ion traps, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) [ 4 , 5 , 6 , 7 , 8 ]. In addition to precursor-fragment correlations, two-dimensional partial correlation mass spectrometry (2D PC MS) has also been developed to explore correlations between complementary fragment ion signals [ 9 ].…”

Phase Correction for Absorption Mode Two-dimensional Mass Spectrometry

“…Two-dimensional mass spectrometry (2D MS) is a method for tandem mass spectrometry that relies on manipulating ion motions to correlate precursor and fragment ion signals [1][2][3]. Various methods for 2D MS have been developed for quadrupolar ion traps, linear ion traps, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) [4][5][6][7][8][9]. In 2D FT-ICR MS, the most frequently used pulse sequence is the one proposed by Pfändler et al to modulate ion radii in the ICR cell before fragmentation [1][2][3]10,11].…”