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

Fouque, Dany Jeanne Dit; Maroto, Alicia; Memboeuf, Antony

doi:10.1002/jms.4698

Cited by 11 publications

(17 citation statements)

References 31 publications

(80 reference statements)

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“…Nevertheless, in the last two decades, many MS/MS strategies have been developed to solve this problem by allowing the characterization and quantification of isomers and/or isobars in mixtures via a standardized approach, applicable to different compounds [ 11 ]. Among these strategies, the most promising and interesting for a widespread application in the recognition of isomers are based on (1) energy-resolved tandem mass experiments [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and (2) kinetics of the ion-molecule interaction [ 20 , 21 , 22 ], even if the latter are limited to the use of the ion trap. Summarizing the reported results, the discrimination between isomers was achieved by optimizing the selection of precursor ion, its fragmentation through collision induced dissociation (CID) mechanism and the analysis of fragmented ions produced.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization

Pallecchi

Braconi

Menicatti

et al. 2022

IJMS

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This paper proposes a tandem mass spectrometry (MS/MS) approach in isomer recognition by playing in the “energetic dimension” of the experiment. The chromatographic set up (HPLC) was tuned to minimize the run time, without requiring high efficiency or resolution between the isomers. Then, the MS/MS properties were explored to solve the signal assignment by performing a series of energy resolved experiments in order to optimize the parameters, and by applying an interesting post-processing data elaboration tool (LEDA). The reliability of the new approach was evaluated, determining the accuracy and precision of the quantitative results through analysis of the isomer mixture solutions. Next, the proposed method was applied in a chemical stability study of human plasma samples through the simultaneous addition of a pair of isomers. In the studied case, only one of the isomers suffered of enzymatic hydrolysis; therefore, the influence of the stable isomer on the degradation rate of the other was verified. In order to monitor this process correctly, it must be possible to distinguish each isomer present in the sample, quantify it, and plot its degradation profile. The reported results demonstrated the effectiveness of the LEDA algorithm in separating the isomers, without chromatographic resolution, and monitoring their behavior in human plasma samples.

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Section: Introductionmentioning

confidence: 99%

Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization

Pallecchi

Braconi

Menicatti

et al. 2022

IJMS

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“…Nonetheless, it might be that a fragment is consistent with two isobars simultaneously from a pure mass loss perspective, e.g., the benzyl fragment C 6 H 5 + could arise from either one (or both) of two co-fragmented aromatic precursors. Only a few studies have explicitly addressed the problem for DI-MS, e.g., it is reported that ion mobility 31 or "collisional purification" 32,33 on MS 3 -or pseudo-MS 3capable instruments can resolve chimeras.…”

Section: Introductionmentioning

confidence: 99%

Resolving isobaric interferences in direct infusion tandem mass spectrometry

Kaeslin

Zenobi

2022

Rapid Comm Mass Spectrometry

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Rationale The co‐fragmentation of precursors in direct infusion (DI) tandem high‐resolution mass spectrometry (HRMS) can complicate the fragment spectra and consequently lead to false hits during compound identification. Methods The method herein described, termed IQAROS (incremental quadrupole acquisition to resolve overlapping spectra), modulates the intensities of precursors and fragments by stepwise movement of the quadrupole isolation window over the mass‐to‐charge (m/z) range of the precursors. The modulated signals are then deconvoluted by a linear regression model to reconstruct the fragment spectra with less interference. The hardware to demonstrate the use of IQAROS was an orbitrap with electrospray ionization (ESI) or secondary electrospray ionization (SESI), although the method can also be applied to other ionization techniques or mass analyzers. Results Assessing the performance of IQAROS with isobaric standards revealed that the reconstructed fragment spectra match with spectra acquired from the pure standards and that more compounds were correctly identified compared with the classical approach with the quadrupole centered at the m/z value of the precursor of interest. Moreover, the strength of IQAROS is exemplified by the identification of two isobaric biomarkers directly from a breath sample with SESI‐HRMS. Conclusions With IQAROS, cleaner fragment spectra of co‐fragmenting isobars during DI‐HRMS analysis can be obtained. IQAROS can easily be set up by the standard graphical user interface of the instrument. Therefore, it facilitates the characterization of features of interest in samples analyzed by DI‐HRMS, for example, in high‐throughput or real‐time metabolomics.

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“…On the other hand, ISF provides an additional collision stage prior to the mass analyzer’s work, which enables acquisition of abundant mass spectral information even from the soft electrospray ionization (ESI) source. ,− Since fragmentation of analytes in ISF is similar to that in CID of tandem mass spectrometry (MS/MS), ,, ISF has been employed as an inexpensive collision-induced fragmentation generator to obtain MS/MS spectra of compounds in a mass spectrometer with only a single-stage mass analyzer. , Therefore, ISF has been used for the characterization of organic compounds and biomacromolecules, such as 1,4-dihydropyridine calcium antagonists and glycopeptides . In recent years, ISF has also been coupled with high resolution mass spectrometry (ISF-HRMS) to screen the compounds that can generate characteristic neutral loss (NL) or fragment ion (FI) in ion source from biological samples. ,− For instance, since some modified metabolites including acetylated, glucosidated, glucuronidated, sulfated, and ribose conjugated can produce specific NL fragments in ion source, an ISF-HRMS method has been developed for profiling metabolites with specific groups in human urine samples .…”

mentioning

confidence: 99%

“…12,15 Therefore, ISF has been used for the characterization of organic compounds and biomacromolecules, such as 1,4-dihydropyridine calcium antagonists 18 and glycopeptides. 19 In recent years, ISF has also been coupled with high resolution mass spectrometry (ISF-HRMS) to screen the compounds that can generate characteristic neutral loss (NL) or fragment ion (FI) in ion source from biological samples. 7,20−23 For instance, since some modified metabolites including acetylated, glucosidated, glucuronidated, sulfated, and ribose conjugated can produce specific NL fragments in ion source, an ISF-HRMS method has been developed for profiling metabolites with specific groups in human urine samples.…”

mentioning

confidence: 99%

Integration of Chemical Derivatization and in-Source Fragmentation Mass Spectrometry for High-Coverage Profiling of Submetabolomes

Zhu

Wang

et al. 2021

Anal. Chem.

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In-source fragmentation-based high-resolution mass spectrometry (ISF-HRMS) is a potential analytical technique, which is usually used to profile some specific compounds that can generate diagnostic neutral loss (NL) or fragment ion (FI) in ion source inherently. However, the ISF-HRMS method does not work for those compounds that cannot inherently produce diagnostic NL or FI in ion source. In this study, a derivatization-based in-source fragmentation-information-dependent acquisition (DISF-IDA) strategy was proposed for profiling the metabolites with easily labeled functional groups (submetabolomes) by liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-Q-TOF MS). As a proof-of-concept study, 36 carboxylated compounds labeled with N,N-dimethylethylenediamine (DMED) were selected as model compounds to examine performance of DISF-IDA strategy in screening the carboxylated metabolites and acquiring their MSn spectra. In ESI source, the DEMD-derived carboxylated compounds were fragmented to produce characteristic neutral losses of 45.0578, 63.0684, and/or 88.1000 Da that were further used as diagnostic features for screening the carboxylated metabolites by DISF-IDA-based LC-Q-TOF MS. Furthermore, high-resolution MSn spectra of the model compounds were also obtained within a single run of DISF-IDA-based LC-Q-TOF MS analysis, which contributed to the improvement of the annotation confidence. To further verify its applicability, DISF-IDA strategy was used for profiling carboxylated submetabolome in mice feces. Using this strategy, a total of 351 carboxylated metabolites were detected from mice feces, of which 178 metabolites (51% of the total) were positively or putatively identified. Moreover, DISF-IDA strategy was also demonstrated to be applicable for profiling other submetabolomes with easily labeled functional groups such as amino, carbonyl, and cis-diol groups. Overall, our proposed DISF-IDA strategy is a promising technique for high-coverage profiling of submetabolomes with easily labeled functional groups in biological samples.

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

Cited by 11 publications

References 31 publications

Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization

Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization

Resolving isobaric interferences in direct infusion tandem mass spectrometry

Integration of Chemical Derivatization and in-Source Fragmentation Mass Spectrometry for High-Coverage Profiling of Submetabolomes

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