The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro‐litre of chimeric mice blood

Gallagher, Richard T.; Dillon, L A; Grimsley, Aidan; Murphy, James Peter; Samuelsson, Kristin; Douce, David

doi:10.1002/rcm.6902

Cited by 23 publications

(10 citation statements)

References 33 publications

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“…Recently Gallagher et al showed that a prototype microfluidic chip-based device coupled with HRMS could be utilized for the identification and quantification of midazolam and associated metabolites in 1 μl samples of mouse blood from control and humanized chimeric mice. The enhanced sensitivity of the method allowed the metabolites that had previously not been observed in samples from chimeric mice to be detected [108].…”

Section: Application Of Integrated Microfluidic (Chipbased) Lc-ms Formentioning

confidence: 98%

“…The application of integrated microfluidic LC or (chipbased LC) with MS for the analysis of biofluid samples has been well documented for the analysis of many different compound classes in biofluids including: glycans, various lipid classes, small molecule drugs, peptides and proteins [83,[90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108]. To date the vast majority of examples of chip-based LC-MS quantification of analytes in biofluids has been carried out using low-resolution mass spectrometers such as tandem quadrupole MS.…”

Section: Application Of Integrated Microfluidic (Chipbased) Lc-ms Formentioning

confidence: 99%

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Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

et al. 2015

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Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited sample volumes and allow multiple analyses from one sample. This is particularly attractive in areas where ultrahigh assay sensitivity, low limits of detection and small sample volumes are becoming commonplace. However, implementation of cLC-MS in the bioanalytical-drug metabolism area had been hampered by the lack of commercial instrumentation and the need for experts to operate the system. Recent advances in microfabricated devices such as chip-cube and ion-key technologies offer the potential for true implementation of cLC in the modern laboratory including the benefits of the combination of this type of separation with high-resolution MS.

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Section: Application Of Integrated Microfluidic (Chipbased) Lc-ms Formentioning

confidence: 98%

Section: Application Of Integrated Microfluidic (Chipbased) Lc-ms Formentioning

confidence: 99%

Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

et al. 2015

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“…High‐performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) is currently the method of choice for metabolite identification and quantification studies for small molecules, peptides and others 1–7 . Improvements in chromatographic separation such as ultra‐high‐performance liquid chromatography (UPLC) have generally led to higher chromatographic resolution, 8 with sharper peaks and correspondingly higher MS sensitivity 9 . A common strategy for MS data acquisition involves data‐dependent acquisition (DDA) in which a list of likely metabolites is employed to drive targeted fragmentation (MS 2 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolite identification using an ion mobility enhanced data‐independent acquisition strategy and automated data processing

Radchenko

Kochansky

Cancilla

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale: Liquid chromatography/mass spectrometry is an essential tool for efficient and reliable quantitative and qualitative analysis and underpins much of contemporary drug metabolism and pharmacokinetics. Data-independent acquisition methods such as MS E have reduced the potential to miss metabolites, but do not formally generate quadrupole-resolved product ion spectra. The addition of ion mobility separation to these approaches, for example, in High-Definition MS E (HDMS E ) has the potential to reduce the time needed to set up an experiment and maximize the chance that all metabolites present can be resolved and characterized.We compared High-Definition Data-Dependent Acquisition (HD-DDA), MS E and HDMS E approaches using automated software processing with Mass-MetaSite and WebMetabase. Methods:Metabolite identification was performed on incubations of glucagon-like peptide-1 (7-37) (GLP-1) and verapamil hydrochloride. The HD-DDA, MS E and HDMS E experiments were conducted on a Waters ACQUITY UPLC I-Class LC system with a VION IMS quadrupole time-of-flight (QTOF) mass spectrometer operating under UNIFI control. All acquired data were processed using MassMetaSite able to read data from UNIFI 1.9.4. WebMetabase was used to review the detected chromatographic peaks and the spectral data interpretations. Results:A comparison of outcomes obtained for MS E and HDMS E data demonstrated that the same structures were proposed for metabolites of both verapamil and GLP-1. The ratio of structurally matched to mismatched product ions found by MassMetaSite was slightly greater for HDMS E than for MS E , and HD-DDA, thus improving confidence in the structures proposed through the addition of ion mobility based data acquisitions . Conclusions: HDMS E data acquisition is an effective approach for the elucidation of metabolite structures for both small molecules and peptides, with excellent accuracy and quality, requiring minimal tailoring for the compound under investigation.

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“…Nano-LC and μLC systems have been developed by several vendors and are quickly gaining popularity. One of these is an integrated μLC-electrospray chip MS interface introduced in 2014, the Waters IonKey/MS™ [16,17]. Applications range from steroids and midazolam to peptides [16,[18][19][20].…”

mentioning

confidence: 99%

Quantitative Bottom Up Analysis of Infliximab in Serum Using Protein A Purification and Integrated μLC-Electrospray Chip Ionkey MS/MS Technology

Kleinnijenhuis¹,

Ingola²,

Toersche³

et al. 2016

Bioanalysis

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The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro‐litre of chimeric mice blood

Cited by 23 publications

References 33 publications

Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

Metabolite identification using an ion mobility enhanced data‐independent acquisition strategy and automated data processing

Quantitative Bottom Up Analysis of Infliximab in Serum Using Protein A Purification and Integrated μLC-Electrospray Chip Ionkey MS/MS Technology

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