Ion mobility spectrometry

Salman, Dahlia; Eiceman, Gary A.; Ruszkiewicz, Dorota; Ruzsányi, Veronika; Brodrick, Emma; Thomas, C. L. Paul

doi:10.1016/b978-0-12-819967-1.00011-6

Cited by 3 publications

(3 citation statements)

References 34 publications

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“…Details about GC-IMS and potential applications in different clinical settings are available in the book 'Ion Mobility Spectrometry' [23] and a recent review [41]. A single breath GC-IMS approach has recently been benchmarked following the 'Peppermint Protocol' [42] and this methodology was assessed for atpatient exhaled thio-VOC determination. The limit of the GC-IMS detector's response was estimated to be 210 fg s −1 .…”

Section: Evaluation Of Gc-ims For Point-of-care Sampling and Analysismentioning

confidence: 99%

Breath markers for therapeutic radiation

et al. 2020

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Radiation dose is important in radiotherapy. Too little, and the treatment is not effective, too much causes radiation toxicity. A biochemical measurement of the effect of radiotherapy would be useful in personalisation of this treatment. This study evaluated changes in exhaled breath volatile organic compounds (VOC) associated with radiotherapy with thermal desorption gas chromatography mass-spectrometry followed by data processing and multivariate statistical analysis. Further the feasibility of adopting gas chromatography ion mobility spectrometry for radiotherapy point-of-care breath was assessed. A total of 62 participants provided 240 end-tidal 1 dm3 breath samples before radiotherapy and at 1, 3, and 6 h post-exposure, that were analysed by thermal-desorption/gas-chromatography/quadrupole mass-spectrometry. Data were registered by retention-index and mass-spectra before multivariate statistical analyses identified candidate markers.A panel of sulfur containing compounds (thio-VOC) were observed to increase in concentration over the 6 h following irradiation. 3-methylthiophene (80 ng.m−3 to 790 ng.m−3) had the lowest abundance while 2-thiophenecarbaldehyde(380 ng.m−3 to 3.85 μg.m−3) the highest; note, exhaled 2-thiophenecarbaldehyde has not been observed previously. The putative tumour metabolite 2,4-dimethyl-1-heptene concentration reduced by an average of 73% over the same time. Statistical scoring based on the signal intensities thio-VOC and 3-methylthiophene appears to reflect individuals’ responses to radiation exposure from radiotherapy. The thio-VOC are hypothesised to derive from glutathione and Maillard-based reactions and these are of interest as they are associated with radio-sensitivity. Further studies with continuous monitoring are needed to define the development of the breath biochemistry response to irradiation and to determine the optimum time to monitor breath for radiotherapy markers. Consequently, a single 0.5 cm3 breath-sample gas chromatography-ion mobility approach was evaluated. The calibrated limit of detection for 3-methylthiophene was 10 μg.m−3 with a lower limit of the detector’s response estimated to be 210 fg.s−1; the potential for a point-of-care radiation exposure study exists.

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Section: Evaluation Of Gc-ims For Point-of-care Sampling and Analysismentioning

confidence: 99%

Breath markers for therapeutic radiation

et al. 2020

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“…A limited number of breath tests, which are based on isotopically labelled probes, are in current use for such clinical diagnosis [9,10]. In these tests, the respective labelled precursor compounds, such as 13 C-pantoprazol for CYP2C19 or 13 C-methacetin for CYP1A2, are metabolised resulting in increases of 13 CO 2 in the exhaled breath, which is measured using infrared spectroscopy [11]. However, the high amount of the isotopically labelled substrates that need to be ingested (several hundred mg) makes the breath test expensive.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the volatile metabolites in exhaled breath should be accessible for detection using clinical friendly analytical platforms in real or near to real-time with a high chemical specificity and selectivity. Analytical instruments such as proton transfer reaction/selective reagent ion-time-of-flight mass spectrometry and fast gas chromatography-ion mobility spectrometry have been demonstrated to be useful for such applications [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Establishing a cell-based screening workflow for determining the efficiency of CYP2C9 metabolism: moving towards the use of breath volatiles in personalised medicine

Lochmann,

Nikolajevic,

Stock

et al. 2023

J. Breath Res.

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The use of volatile biomarkers in exhaled breath as predictors to individual drug response would advance the field of personalized medicine by providing direct information on enzyme activity. This would result in enormous benefits, both for patients and the healthcare sector. Non-invasive breath tests would also gain a high acceptance by patients. Towards this goal, differences in metabolism resulting from extensive polymorphisms in a major group of drug-metabolizing enzymes, the cytochrome P450 (CYP) family, need to be determined and quantified. CYP2C9 is responsible for metabolising many crucial drugs (e.g., diclofenac) and food ingredients (e.g., limonene). In this paper, we provide a proof-of-concept study that illustrates the in vitro bioconversion of diclofenac in recombinant HEK293T cells overexpressing CYP2C9 to 4’-hydroxydiclofenac. This in vitro approach is a necessary and important first step in the development of breath tests to determine and monitor metabolic processes in the human body. By focusing on the metabolic conversion of diclofenac, we have established a workflow using a cell-based system for CYP2C9 activity. Using limonene, we illustrate how the bioconversion of diclofenac can be limited in the presence of another CYP2C9 metabolising substrate, with increasing limonene levels continuously reducing the formation of 4’-hydroxydiclofenac. Michaelis-Menten kinetics were performed for the diclofenac 4'-hydroxylation, with and without limonene, giving a kinetic constant of the reaction, KM, of 103 µM and 94.1 µM, respectively, and a maximum reaction rate, Vmax, of 46.8 pmol min-1 106 cells-1 and 56.0 pmol min-1 106 cells-1 with and without the inhibitor, respectively, suggesting a non-competitive or mixed inhibition type. The half maximal inhibitory concentration value (IC50) for the inhibition of the formation of 4’-hydroxydiclofenace by limonene is determined to be 1413 µM.

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