Ion trap MS using high trapping gas pressure enables unequivocal structural analysis of three isobaric compounds in a mixture by using energy‐resolved mass spectrometry and the survival yield technique

Abstract

Recently, it has been shown that energy‐resolved mass spectrometry (MS) can provide quantitative information from two isomeric or isobaric compounds in mixtures by using the survival yield (SY) technique together with “gas‐phase collisional purification” (GPCP) strategy (Anal. Chem., 2016, 88, p.10821). Herein, we present an improvement and an extension of this concept to the structural analysis of a model mixture of three isobaric compounds (two peptides and a polyether). By using default collision‐induced dissociation (CID) tandem MS parameters on an ion trap instrument, the previous approach did not show any signs of isobaric contamination. However, by modifying CID conditions and using a threefold increase of the He trapping gas pressure (to reach 3.00·10−5 mbar), the SY curve was unexpectedly and strongly shifted to higher excitation voltages with two plateaus appearing. Those plateaus, indicating clearly the presence of three isobaric compounds, were taken as reliable indicators to perform GPCP at carefully selected excitation voltages in order to selectively fragment one compound after the other. In this way, CID mass spectra of each compound were correctly recovered, both in terms of fragment ion peaks and in terms of relative intensities, from energy‐resolved MSn spectra of the three compounds mixture. This feature enables their unequivocal structural analysis as if samples were free from isobaric interferences. In this paper, we also discuss the possibility for recovering SY curves for pure compounds directly from the mixture. Clearly, in this case, the higher He trapping gas pressure made it possible to use the SY technique, for the first time, for the structural analysis in the case of mixtures of three isobaric compounds. This observation, quite unexpected, demonstrates that the trapping gas pressure is of paramount importance although it is usually not considered in energy‐resolved MS for structural and/or quantitative analysis.

Structural analysis of a compound despite the presence of an isobaric interference by using in‐source Collision Induced Dissociation and tandem mass spectrometry

“…However, to do GPCP, two conditions must be fulfilled: at first, large enough difference in the energetics of fragmentation between the iso‐baric/meric interference and the analyte is required (the necessary difference depending on the experimental conditions 14 ). Second, multistage mass spectrometry is necessary to perform the two successive isolation stages.…”

“…In this context, SY curves were used as an indicator of iso‐baric/meric contamination and to provide information not only for quantification purposes but also for structural analysis. Thanks to the presence of this plateau, we have shown that the structural analysis of two 6 and, more recently, up to three isobaric compounds 14 can be performed. Two kinds of information can be obtained from this plateau: (1) its vertical position provides the relative gas‐phase abundances of the mixture of compounds, 6,8,12–15 and (2) the corresponding collision voltage provides valuable information to perform a new strategy, which we have called the gas‐phase collisional purification (GPCP) 15 .…”

“…Thanks to the presence of this plateau, we have shown that the structural analysis of two 6 and, more recently, up to three isobaric compounds 14 can be performed. Two kinds of information can be obtained from this plateau: (1) its vertical position provides the relative gas‐phase abundances of the mixture of compounds, 6,8,12–15 and (2) the corresponding collision voltage provides valuable information to perform a new strategy, which we have called the gas‐phase collisional purification (GPCP) 15 . The latter was shown to allow for the collisional purification of the analyte from the interference and for its structural analysis as though it were free from interference 12–15 .…”

“…SY curves of pure compounds are indeed usually sigmoidal. However, in the presence of an iso‐baric/meric interference, the SY curve may be distorted, showing a hump or even a plateau if the fragmentation parameters of the two compounds are different enough 6,8,12–14 . In this context, SY curves were used as an indicator of iso‐baric/meric contamination and to provide information not only for quantification purposes but also for structural analysis.…”

Determination of coeluted isomers in wine samples by application of MS/MS deconvolution analysis

“…In several recent studies, it has been shown that unequivocal structural and quantitative analysis of an isobaric/isomeric compound in model mixtures can be performed using tandem mass spectrometry methods, such as the Cooks' kinetic method, [7][8][9] and, more recently, energy-resolved mass spectrometry (ERMS) and the survival yield (SY) technique. [10][11][12][13][14][15][16][17] The aim of this study was to propose a simple and rapid quantitative determination of the IPMA isomers, based on a series of ERMS experiments. This approach achieved clear differentiation between the isomers, but, to obtain an even better distinction, we processed the MS/MS spectra data of the isomers using a mathematical algorithm, (LEDA), which consists of the application of a matrix of linear regression equations to different experimental data.…”