Untargeted Differential Metabolomics Analysis Using Drift Tube Ion Mobility-Mass Spectrometry

Reisdorph, Rick; Michel, Cole; Quinn, Kevin; Doenges, Katrina; Reisdorph, Nichole

doi:10.1007/978-1-0716-0030-6_3

Cited by 11 publications

(11 citation statements)

References 11 publications

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“…For sake of comparison with gold standard in feature annotation in metabolomics, collisional cross section are among the most reproducible parameters with interlaboratory variation in the range of 2% 36,41,53 and 5% and are usually the threshold for identification confirmation. 6,54 Although HILIC is a powerful method to separate polar compounds, deviation of the retention time up to 10% to in-house databases are usually considered for feature annotation. 6 As a first approach, we propose that such a scoring system can be based on different ranges of bias between μ eff measurements and μ eff values in databases (Table 1).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Capillary Electrophoresis-Mass Spectrometry at Trial by Metabo-Ring: Effective Electrophoretic Mobility for Reproducible and Robust Compound Annotation

et al. 2020

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Capillary zone electrophoresis-mass spectrometry (CE-MS) is a mature analytical tool for the efficient profiling of (highly) polar and ionizable compounds. However, the use of CE-MS in comparison to other separation techniques remains underrepresented in metabolomics, as this analytical approach is still perceived as technically challenging and less reproducible, notably for migration time. The latter is key for a reliable comparison of metabolic profiles and for unknown biomarker identification that is complementary to high resolution MS/MS. In this work, we present the results of a Metabo-ring trial involving 16 CE-MS platforms among 13 different laboratories spanning two continents. The goal was to assess the reproducibility and identification capability of CE-MS by employing effective electrophoretic mobility (μ eff ) as the key parameter in comparison to the relative migration time (RMT) approach. For this purpose, a representative cationic metabolite mixture in water, pretreated human plasma, and urine samples spiked with the same metabolite mixture were used and distributed for analysis by all laboratories. The μ eff was determined for all metabolites spiked into each sample. The background electrolyte (BGE) was prepared and employed by each participating lab following the same protocol. All other parameters (capillary, interface, injection volume, voltage ramp, temperature, capillary conditioning, and rinsing procedure, etc.) were left to the discretion of the contributing laboratories. The results revealed that the reproducibility of the μ eff for 20 out of the 21 model compounds was below 3.1% vs 10.9% for RMT, regardless of the huge heterogeneity in experimental conditions and platforms across the 13 laboratories. Overall, this Metabo-ring trial demonstrated that CE-MS is a viable and reproducible approach for metabolomics.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Capillary Electrophoresis-Mass Spectrometry at Trial by Metabo-Ring: Effective Electrophoretic Mobility for Reproducible and Robust Compound Annotation

et al. 2020

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“…All spectra were acquired using a pseudorandom 4-bit multiplexing sequence (“multiplexed mode”), which has been described in detail previously. − Briefly, ion packets are sequentially gated into the drift tube at predetermined intervals and traverse the region as normal (e.g., eight packets are injected during one scan interval). The overlapping spectra are deconvoluted and combined postacquisition based on the pseudorandom gate timing using the PNNL PreProcessor software package (v.2021.04.21) developed at Pacific Northwest National Lab (PNNL, ) .…”

Section: Experimental Sectionmentioning

confidence: 99%

Improving the Speed and Selectivity of Newborn Screening Using Ion Mobility Spectrometry–Mass Spectrometry

Dodds

Baker

2021

Anal. Chem.

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Detection and diagnosis of congenital disorders is the principal aim of newborn screening (NBS) programs worldwide. Mass spectrometry (MS) has become the preferred primary testing method for high-throughput NBS sampling because of its speed and selectivity. However, the ever-increasing list of NBS biomarkers included in expanding panels creates unique analytical challenges for multiplexed MS assays due to isobaric/isomeric overlap and chimeric fragmentation spectra. Since isobaric and isomeric systems limit the diagnostic power of current methods and require costly follow-up exams due to many false-positive results, here, we explore the utility of ion mobility spectrometry (IMS) to enhance the accuracy of MS assays for primary (tier 1) screening. Our results suggest that ∼400 IMS resolving power would be required to confidently assess most NBS biomarkers of interest in dried blood spots (DBSs) that currently require follow-up testing. While this level of selectivity is unobtainable with most commercially available platforms, the separations detailed here for a commercially available drift tube IMS (Agilent 6560 with high-resolution demultiplexing, HRdm) illustrate the unique capabilities of IMS to separate many diagnostic NBS biomarkers from interferences. Furthermore, to address the need for increased speed of NBS analyses, we utilized an automated solid-phase extraction (SPE) system for ∼10 s sampling of simulated NBS samples prior to IMS-MS. This proof-of-concept work demonstrates the unique capabilities of SPE-IMS-MS for high-throughput sample introduction and enhanced separation capacity conducive for increasing speed and accuracy for NBS.

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“…The addition of metal ions such as copper and zinc to the sample resulted in complexes that had differentiated mobilities and, thus, were separable by DTIMS [83]. Ion mobility has also shown to be an interesting option for the analysis of metabolites in biological samples for metabolite profiling, the so-called metabolomics [84][85][86][87]. As an example, Zhang and coworkers compared three different operation modes, namely FIA/IM-MS, LC-MS, and LC-IM-MS for metabolomics analyses of human plasma and HaCaT cells using DTIMS [85].…”

Section: Drift Tube Ion Mobility Spectrometry (Dtims)mentioning

confidence: 99%

“…CCS determination has also been demonstrated to be useful in metabolomics since it can aid in the small molecule identification for both targeted and untargeted metabolite screening [87]. Reisdorph and coworkers described a typical DTIMS metabolomics workflow as a proposal to investigators who are interested in using IM-MS in their metabolomic studies [84].…”

Section: Drift Tube Ion Mobility Spectrometry (Dtims)mentioning

confidence: 99%

Ion Mobility–Mass Spectrometry for Bioanalysis

et al. 2021

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This paper aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased. This paper introduces the reader to the principles controlling the separation in IMS and reviews recent applications using this technique in the field of bioanalysis.

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Untargeted Differential Metabolomics Analysis Using Drift Tube Ion Mobility-Mass Spectrometry

Cited by 11 publications

References 11 publications

Capillary Electrophoresis-Mass Spectrometry at Trial by Metabo-Ring: Effective Electrophoretic Mobility for Reproducible and Robust Compound Annotation

Capillary Electrophoresis-Mass Spectrometry at Trial by Metabo-Ring: Effective Electrophoretic Mobility for Reproducible and Robust Compound Annotation

Improving the Speed and Selectivity of Newborn Screening Using Ion Mobility Spectrometry–Mass Spectrometry

Ion Mobility–Mass Spectrometry for Bioanalysis

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