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      Targeted and untargeted metabolomics and lipidomics in dried blood microsampling: Recent applications and perspectives

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          Abstract

          Blood microsampling (BµS) offers an alternative to conventional methods that use plasma or serum for profiling human health, being minimally invasive and cost effective, especially beneficial for vulnerable populations. We present a non‐systematic review that offers a synopsis of the analytical methods, applications and perspectives related to dry blood microsampling in targeted and untargeted metabolomics and lipidomics research in the years 2022 and 2023. BµS shows potential in neonatal and paediatric studies, therapeutic drug monitoring, metabolite screening, biomarker research, sports supervision, clinical disorders studies and forensic toxicology. Notably, dried blood spots and volumetric absorptive microsampling options have been more extensively studied than other volumetric technologies. Therefore, we suggest that a further investigation and application of the volumetric technologies will contribute to the use of BµS as an alternative to conventional methods. Conversely, we support the idea that harmonisation of the analytical methods when using BµS would have a positive impact on its implementation.

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          Most cited references103

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          Ion suppression; a critical review on causes, evaluation, prevention and applications.

          The consequences of matrix effects in mass spectrometry analysis are a major issue of concern to analytical chemists. The identification of any ion suppressing (or enhancing) agents caused by sample matrix, solvent or LC-MS system components should be quantified and measures should be taken to eliminate or reduce the problem. Taking account of ion suppression should form part of the optimisation and validation of any quantitative LC-MS method. For example the US Food and Drug Administration has included the evaluation of matrix effects in its "Guidance for Industry on Bioanalytical Method Validation" (F.D.A. Department of Health and Human Services, Guidance for industry on bioanalytical method validation, Fed. Regist. 66 (100) 2001). If ion suppression is not assessed and corrected in an analytical method, the sensitivity of the LC-MS method can be seriously undermined, and it is possible that the target analyte may be undetected even when using very sensitive instrumentation. Sample analysis may be further complicated in cases where there are large sample-to-sample matrix variations (e.g. blood samples from different people can sometimes vary in certain matrix components, shellfish tissue samples sourced from different regions where different phytoplankton food sources are present, etc) and therefore exhibit varying ion-suppression effects. Although it is widely agreed that there is no generic method to overcome ion suppression, the purpose of this review is to: provide an overview of how ion suppression occurs, outline the methodologies used to assess and quantify the impact of ion suppression, discuss the various corrective actions that have been used to eliminate ion suppression in sample analysis, that is to say the deployment of techniques that eliminate or reduce the components in the sample matrix that cause ion suppression. This review article aims to collect together the latest information on the causes of ion suppression in LC-MS analysis and to consider the efficacy of common approaches to eliminate or reduce the problem using relevant examples published in the literature. © 2013 Elsevier B.V. All rights reserved.
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            Hemato-critical issues in quantitative analysis of dried blood spots: challenges and solutions.

            Dried blood spot (DBS) sampling for quantitative determination of drugs in blood has entered the bioanalytical arena at a fast pace during the last decade, primarily owing to progress in analytical instrumentation. Despite the many advantages associated with this new sampling strategy, several issues remain, of which the hematocrit issue is undoubtedly the most widely discussed challenge, since strongly deviating hematocrit values may significantly impact DBS-based quantitation. In this review, an overview is given of the different aspects of the 'hematocrit problem' in quantitative DBS analysis. The different strategies that try to cope with this problem are discussed, along with their potential and limitations. Implementation of some of these strategies in practice may help to overcome this important hurdle in DBS assays, further allowing DBS to become an established part of routine quantitative bioanalysis.
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              The effect of hematocrit and punch location on assay bias during quantitative bioanalysis of dried blood spot samples.

              Dried blood spot (DBS) sampling, the collection of whole blood samples on paper, is being evaluated for its use in quantitative analysis. The aim of this investigation was to evaluate the impact of sample hematocrit (HCT) and punch location on assay bias in the measurement of compounds with varying physicochemical properties, when a portion of a DBS sample is analyzed. In addition, the statistical significance of factors such as compound, card type, HCT level, spot position on a card and the location of the punch on the spot were evaluated. The results of this work indicate that for quantitative analysis using a portion of the DBS, notable bias (>15%) exists due to the effect of HCT and nonhomogeneous distribution of compound across the spot. The statistical analysis of results from a split-split-plot designed study showed that the factors of compound, card type and HCT were statistically significant (p < 0.05) both individually and in complex interactions, which affect the accuracy of quantitative concentrations obtained from DBS samples for each compound on each card type. To achieve the acceptance criteria (±15%) for accuracy when removing a portion of the DBS spot for quantitative analysis, HCT and punch location for each selected card type will need to be assessed during validation and sample analysis.
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                Author and article information

                Contributors
                michael.witting@helmholtz-muenchen.de
                Journal
                Anal Sci Adv
                Anal Sci Adv
                10.1002/(ISSN)2628-5452
                ANSA
                Analytical Science Advances
                John Wiley and Sons Inc. (Hoboken )
                2628-5452
                14 June 2024
                June 2024
                : 5
                : 5-6 , Special Issue: Novel Sensors for Food Analysis and Advances in Metabolomics ( doiID: 10.1002/ansa.v5.5-6 )
                : e2400002
                Affiliations
                [ 1 ] Metabolomics and Proteomics Core Helmholtz Zentrum München Neuherberg Germany
                [ 2 ] Afekta Technologies Ltd. Kuopio Finland
                [ 3 ] School of Pharmacy Faculty of Health Sciences University of Eastern Finland Kuopio Finland
                [ 4 ] Centro de Metabolómica y Bioanálisis (CEMBIO) Facultad de Farmacia Universidad San Pablo‐CEU CEU Universities Urbanización Montepríncipe Boadilla del Monte Madrid Spain
                [ 5 ] Department of Metabolism Digestion and Reproduction Imperial College London London UK
                [ 6 ] Chair of Analytical Food Chemistry TUM School of Life Sciences Technical University of Munich Freising‐Weihenstephan Germany
                Author notes
                [*] [* ] Correspondence

                Michael Witting, Metabolomics and Proteomics Core, Helmholtz Zentrum München, Neuherberg, Germany.

                Email: michael.witting@ 123456helmholtz-muenchen.de

                Author information
                https://orcid.org/0000-0002-1462-4426
                Article
                ANSA202400002
                10.1002/ansa.202400002
                11210747
                1d0fd526-0262-4bc9-ad68-719f6b594fc8
                © 2024 The Author(s). Analytical Science Advances published by Wiley‐VCH GmbH.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 May 2024
                : 26 January 2024
                : 14 May 2024
                Page count
                Figures: 1, Tables: 9, Pages: 27, Words: 15741
                Funding
                Funded by: HORIZON EUROPE Marie Sklodowska‐Curie Actions , doi 10.13039/100018694;
                Award ID: 101073062
                Categories
                Review
                Review
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:27.06.2024

                blood microsampling,dried blood,lc–ms analysis,lipidomics,metabolomics,targeted and untargeted

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