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      Tear Film Steroid Profiling in Dry Eye Disease by Liquid Chromatography Tandem Mass Spectrometry

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dry eye disease (DED) is a multifactorial disorder of the ocular surface unit resulting in eye discomfort, visual disturbance, and ocular surface damage; the risk of DED increases with age in both sexes, while its incidence is higher among females caused by an overall hormonal imbalance. The role of androgens has recently investigated and these hormones were considered to have a protective function on the ocular surface. In order to correlate DED to tear steroid levels, a robust, specific, and selective method for the simultaneous quantification of cortisol (CORT), corticosterone (CCONE), 11-deoxycortisol (11-DECOL), 4-androstene-3,17-dione (ADIONE), testosterone (TESTO), 17α-hydroxyprogesterone (17-OHP), and progesterone (PROG) was developed and applied for the analysis of tear samples. The method involves a simple extraction procedure of steroids from tears collected on Schirmer strips, followed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In total, tear samples from 14 DED female patients and 13 healthy female controls were analysed and, CORT, ADIONE, and 17-OHP response levels resulted significantly decreased in dry eye patients respect to controls. The receiver operating characteristic (ROC) curve obtained by the combination of these three steroids (AUC = 0.964) demonstrated the good diagnostic power of the differential tear steroids in identifying DED. In conclusion, the present method made it possible, for the first time, to study steroid profiling directly in tear fluid.

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          MetaboAnalyst: a web server for metabolomic data analysis and interpretation

          Jianguo Xia, Nick Psychogios, Nelson Young … (2009)
          Metabolomics is a newly emerging field of ‘omics’ research that is concerned with characterizing large numbers of metabolites using NMR, chromatography and mass spectrometry. It is frequently used in biomarker identification and the metabolic profiling of cells, tissues or organisms. The data processing challenges in metabolomics are quite unique and often require specialized (or expensive) data analysis software and a detailed knowledge of cheminformatics, bioinformatics and statistics. In an effort to simplify metabolomic data analysis while at the same time improving user accessibility, we have developed a freely accessible, easy-to-use web server for metabolomic data analysis called MetaboAnalyst. Fundamentally, MetaboAnalyst is a web-based metabolomic data processing tool not unlike many of today's web-based microarray analysis packages. It accepts a variety of input data (NMR peak lists, binned spectra, MS peak lists, compound/concentration data) in a wide variety of formats. It also offers a number of options for metabolomic data processing, data normalization, multivariate statistical analysis, graphing, metabolite identification and pathway mapping. In particular, MetaboAnalyst supports such techniques as: fold change analysis, t-tests, PCA, PLS-DA, hierarchical clustering and a number of more sophisticated statistical or machine learning methods. It also employs a large library of reference spectra to facilitate compound identification from most kinds of input spectra. MetaboAnalyst guides users through a step-by-step analysis pipeline using a variety of menus, information hyperlinks and check boxes. Upon completion, the server generates a detailed report describing each method used, embedded with graphical and tabular outputs. MetaboAnalyst is capable of handling most kinds of metabolomic data and was designed to perform most of the common kinds of metabolomic data analyses. MetaboAnalyst is accessible at http://www.metaboanalyst.ca
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            Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.

            B Matuszewski, M L Constanzer, C. M. Chavez-Eng (2003)
            In recent years, high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection has been demonstrated to be a powerful technique for the quantitative determination of drugs and metabolites in biological fluids. However, the common and early perception that utilization of HPLC-MS/MS practically guarantees selectivity is being challenged by a number of reported examples of lack of selectivity due to ion suppression or enhancement caused by the sample matrix and interferences from metabolites. In light of these serious method liabilities, questions about how to develop and validate reliable HPLC-MS/MS methods, especially for supporting long-term human pharmacokinetic studies, are being raised. The central issue is what experiments, in addition to the validation data usually provided for the conventional bioanalytical methods, need to be conducted to confirm HPLC-MS/MS assay selectivity and reliability. The current regulatory requirements include the need for the assessment and elimination of the matrix effect in the bioanalytical methods, but the experimental procedures necessary to assess the matrix effect are not detailed. Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described in this paper. Using as an example a set of validation experiments performed for one of our investigational new drug candidates, the concepts of the quantitative assessment of the "absolute" versus "relative" matrix effect are introduced. In addition, experiments for the determination of, the "true" recovery of analytes using HPLC-MS/MS are described eliminating the uncertainty about the effect of matrix on the determination of this commonly measured method parameter. Determination of the matrix effect allows the assessment of the reliability and selectivity of an existing HPLC-MS/MS method. If the results of these studies are not satisfactory, the parameters determined may provide a guide to what changes in the method need to be made to improve assay selectivity. In addition, a direct comparison of the extent of the matrix effect using two different interfaces (a heated nebulizer, HN, and ion spray, ISP) under otherwise the same sample preparation and chromatographic conditions was made. It was demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed.
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              The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007).

              (2007)
              The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop summarizes current knowledge on the epidemiology of dry eye disease, providing prevalence and incidence data from various populations. It stresses the need to expand epidemiological studies to additional geographic regions, to incorporate multiple races and ethnicities in future studies, and to build a consensus on dry eye diagnostic criteria for epidemiological studies. Recommendations are made regarding several characteristics of dry eye questionnaires that might be suitable for use in epidemiological studies and randomized controlled clinical trials. Risk factors for dry eye and morbidity of the disease are identified, and the impact of dry eye disease on quality of life and visual function are outlined. Suggestions are made for further prospective research that would lead to improvement of both eye and general public health.
              Article 0 comments Cited 300 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 24 June 2017
                Publication date Collection: July 2017
                Volume: 18
                Issue: 7
                Electronic Location Identifier: 1349
                Affiliations
                [1 ]Department of Medical Oral and Biotechnological Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy; mirco.zucchelli@ 123456unich.it (M.Z.); ps@ 123456unich.it (P.S.); claudia.rossi@ 123456unich.it (C.R.)
                [2 ]Analytical Biochemistry and Proteomics Laboratory, Research Centre on Aging and Translational Medicine (Ce.S.I-MeT), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy; ilaria.cicalini@ 123456unich.it (I.C.); p.delboccio@ 123456unich.it (P.D.B.)
                [3 ]Opthalmic Clinic, Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy; l.agnifili@ 123456unich.it (L.A.); roberta.calienno@ 123456gmail.com (R.C.); leonardo.mastropasqua@ 123456unich.it (L.M.)
                [4 ]Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
                Author notes
                [* ]Correspondence: dpieragostino@ 123456unich.it ; Tel.: +39-0871-541-593; Fax: +39-0871-541-598
                Author information
                https://orcid.org/0000-0003-1015-3484
                Article
                Publisher ID: ijms-18-01349
                DOI: 10.3390/ijms18071349
                PMC ID: 5535842
                PubMed ID: 28672794
                SO-VID: a0b4be0b-5ef5-4296-a1cf-3cd5f4add388
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 April 2017
                Date accepted : 22 June 2017
                Categories
                Subject: Article

                ScienceOpen disciplines: Molecular biology
                Keywords: dry eye disease,tears,steroids,mass spectrometry,biomarkers,lc-ms/ms
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: dry eye disease, tears, steroids, mass spectrometry, biomarkers, lc-ms/ms

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