{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:42:23Z","timestamp":1780656143785,"version":"3.54.1"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>During heat sterilization of glucose solutions, a variety of glucose degradation products (GDPs) may be formed. GDPs can cause cytotoxic effects after parenteral administration of these solutions. The aim of the current study therefore was to develop a simple and quick high-performance thin-layer chromatography (HPTLC) method by which the major GDPs can be identified and (summarily) quantified in glucose solutions for parenteral administration. All GDPs were derivatized with o-phenylenediamine (OPD). The resulting GDP derivatives (quinoxalines) were applied to an HPTLC plate. After 20 minutes of chamber saturation with the solvent, the HPTLC plate was developed in a mixture of 1,4-dioxane-toluene-glacial acetic acid (49:49:2, v\/v\/v), treated with thymol-sulfuric acid spray reagent, and heated at 130\u00b0C for 10 minutes. Finally, the GDPs were quantified by using a TLC scanner. For validation, the identities of the quinoxaline derivatives were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS\/MS). Glyoxal (GO)\/methylglyoxal (MGO) and 3-deoxyglucosone (3-DG)\/3-deoxygalactosone (3-DGal) could be identified and quantified in pairs, glucosone (2-KDG), 5-hydroxymethylfurfural (5-HMF), and 3,4-dideoxyglucosone-3-ene (3,4-DGE) each individually. For 2-KDG, the linearity of the method was demonstrated in the range of 1\u201350 \u03bcg\/mL, for 5-HMF and 3,4-DGE 1\u201375 \u03bcg\/mL, for GO\/MGO 2\u2013150 \u03bcg\/mL, and for 3-DG\/3-DGal 10\u2013150 \u03bcg\/mL. All GDPs achieved a limit of detection (LOD) of 2 \u03bcg\/mL or less and a limit of quantification (LOQ) of 10 \u03bcg\/mL or less. R<jats:sup>2<\/jats:sup> was 0.982 for 3.4-DGE, 0.997 for 5-HMF, and 0.999 for 2-KDG, 3-DG\/3-DGal, and GO\/MGO. The intraday precision was between 0.4 and 14.2% and the accuracy, reported as % recovery, between 86.4 and 112.7%. The proposed HPTLC method appears to be an inexpensive, fast, and sufficiently sensitive approach for routine quantitative analysis of GDPs in heat-sterilized glucose solutions.<\/jats:p>","DOI":"10.1371\/journal.pone.0253811","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T18:24:55Z","timestamp":1625250295000},"page":"e0253811","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification and quantification of glucose degradation products in heat-sterilized glucose solutions for parenteral use by thin-layer chromatography"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-4168","authenticated-orcid":true,"given":"Sarah","family":"Leitzen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-3900","authenticated-orcid":true,"given":"Matthias","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Engels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Zapf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Brandl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"issue":"1","key":"pone.0253811.ref001","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-12296-5","article-title":"Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts","volume":"7","author":"J Haybrard","year":"2017","journal-title":"Scientific Reports"},{"key":"pone.0253811.ref002","volume-title":"Standardzulassungen","author":"Erg.-Lfg","year":"2005"},{"issue":"4","key":"pone.0253811.ref003","first-page":"917","article-title":"Stability of amiodarone hydrochloride in admixtures with other injectable drugs","volume":"43","author":"S Campbell","year":"1986","journal-title":"American Journal of Hospital Pharmacy"},{"issue":"10","key":"pone.0253811.ref004","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/jps.2600581018","article-title":"Effect of polysorbate 80 on the solubility and in vivo availability of 2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride (SK&F 33134-a)","volume":"58","author":"LJ Ravin","year":"1969","journal-title":"Journal of Pharmaceutical Sciences"},{"key":"pone.0253811.ref005","first-page":"619","author":"Council of Europe","year":"2019","journal-title":"European Pharmacopoeia 10.0. 511 Methods of Preparation of Sterile Products Strasbourg: European Directorate for the Quality of Medicines"},{"key":"pone.0253811.ref006","author":"European Medicines Agency","year":"2019","journal-title":"Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container"},{"issue":"7","key":"pone.0253811.ref007","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s00134-010-1873-x","article-title":"Infusion fluids contain harmful glucose degradation products","volume":"36","author":"A Bryland","year":"2010","journal-title":"Intensive Care Medicine"},{"issue":"3","key":"pone.0253811.ref008","first-page":"290","article-title":"3-Deoxyglucosone, a promoter of advanced glycation end products in fluids for peritoneal dialysis","volume":"18","author":"T Linden","year":"1998","journal-title":"Peritoneal Dialysis International"},{"issue":"4","key":"pone.0253811.ref009","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/089686080402400415","article-title":"Temperature: The Single Most Important Factor for Degradation of Glucose Fluids during Storage","volume":"24","author":"P Kjellstrand","year":"2004","journal-title":"Peritoneal Dialysis International"},{"issue":"4","key":"pone.0253811.ref010","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s00216-011-5195-9","article-title":"Quantification of the six major alpha-dicarbonyl contaminants in peritoneal dialysis fluids by UHPLC\/DAD\/MSMS","volume":"401","author":"S Mittelmaier","year":"2011","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"pone.0253811.ref011","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1177\/089686080002002S10","article-title":"Can we prevent the degradation of glucose in peritoneal dialysis solutions?","volume":"20","author":"I Ledebo","year":"2000","journal-title":"Peritoneal Dialysis International"},{"issue":"8","key":"pone.0253811.ref012","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/bmc.1194","article-title":"Development and validation of an HPLC method to quantify 3,4-dideoxyglucosone-3-ene in peritoneal dialysis fluids","volume":"23","author":"M Frischmann","year":"2009","journal-title":"Biomedical Chromatography"},{"key":"pone.0253811.ref013","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/089686080002002S06","article-title":"Chemistry of glucose and biochemical pathways of biological interest","volume":"20","author":"M Pischetsrieder","year":"2000","journal-title":"Peritoneal Dialysis International"},{"issue":"5","key":"pone.0253811.ref014","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.neurobiolaging.2009.04.016","article-title":"Advanced glycation endproducts and their receptor RAGE in Alzheimer\u2019s disease","volume":"32","author":"V Srikanth","year":"2011","journal-title":"Neurobiology of Aging"},{"issue":"7","key":"pone.0253811.ref015","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.exger.2007.03.006","article-title":"Advanced glycation endproducts: A biomarker for age as an outcome predictor after cardiac surgery?","volume":"42","author":"A Simm","year":"2007","journal-title":"Experimental Gerontology"},{"issue":"5","key":"pone.0253811.ref016","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1177\/089686080502500502","article-title":"Impact of Glucose in Peritoneal Dialysis: Saint or Sinner?","volume":"25","author":"T Sitter","year":"2005","journal-title":"Peritoneal Dialysis International"},{"issue":"1","key":"pone.0253811.ref017","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/ki.1997.22","article-title":"Immunohistochemical detection of advanced glycosylation end-products in the peritoneum and its possible pathophysiological role in CAPD","volume":"51","author":"M Nakayama","year":"1997","journal-title":"Kidney International"},{"issue":"1","key":"pone.0253811.ref018","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2710.1982.tb00903.x","article-title":"A chromatographic quality control procedure based on HPLC for 5-hydroxymethylfurfural in autoclaved D-glucose infusion fluids","volume":"7","author":"CT Hung","year":"1982","journal-title":"Journal of Clinical Pharmacy and Therapeutics"},{"key":"pone.0253811.ref019","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0021-9673(01)93992-5","article-title":"Reversed-phase high-performance liquid chromatographic method for the quantification of 5-hydroxymethylfurfural as the major degradation product of glucose in infusion fluids","volume":"467","author":"AP Cook","year":"1989","journal-title":"Journal of Chromatography A"},{"issue":"4","key":"pone.0253811.ref020","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0731-7085(87)80036-5","article-title":"Various techniques for the routine evaluation of the degradation of glucose in parenteral solutions\u2014a critical study","volume":"5","author":"E Postaire","year":"1987","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"pone.0253811.ref021","first-page":"2758","volume-title":"European Pharmacopoeia 10.0. Glucose","author":"Council of Europe","year":"2019"},{"key":"pone.0253811.ref022","doi-asserted-by":"crossref","first-page":"9703","DOI":"10.1007\/s00216-013-7162-0","article-title":"Quantification of AICAR-ribotide concentrations in red blood cells by means of LC-MSMS","volume":"405","author":"A Thomas","year":"2013","journal-title":"Analytical and Bioanalytical Chemistry"},{"issue":"4","key":"pone.0253811.ref023","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3747\/pdi.2011.00072","article-title":"A New Neutral-pH Low-GDP Peritoneal Dialysis Fluid","volume":"32","author":"R Himmele","year":"2012","journal-title":"Peritoneal Dialysis International"},{"key":"pone.0253811.ref024","first-page":"28","article-title":"New pH-Neutral Peritoneal Dialysis Solution, Low in Glucose Degradation Products, in a Double-Chamber Bag","volume":"26","author":"J Diaz\u2013Buxo","year":"2010","journal-title":"Advances in Peritoneal Dialysis"},{"key":"pone.0253811.ref025","author":"European Medicines Agency","year":"1995","journal-title":"ICH Topic Q 2 (R1) Validation of Analytical Procedures: Text and Methodology"},{"issue":"8","key":"pone.0253811.ref026","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1021\/tx500153n","article-title":"Structure- and concentration-specific assessment of the physiological reactivity of \u03b1-dicarbonyl glucose degradation products in peritoneal dialysis fluids","volume":"27","author":"L Distler","year":"2014","journal-title":"Chemical Research in Toxicology"},{"issue":"41","key":"pone.0253811.ref027","doi-asserted-by":"crossref","first-page":"28676","DOI":"10.1074\/jbc.M114.563593","article-title":"Extending the Spectrum of \u03b1-Dicarbonyl Compounds in Vivo*","volume":"289","author":"C Henning","year":"2014","journal-title":"The Journal of Biological Chemistry"},{"issue":"1","key":"pone.0253811.ref028","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00217-015-2517-8","article-title":"Formation of \u03b1\u2011dicarbonyl compounds in cookies made from wheat, hull\u2011less barley and colored corn and its relation with phenolic compounds, free amino acids and sugars","volume":"242","author":"T Kocadagli","year":"2016","journal-title":"European Food Research and Technology"},{"issue":"11\u201312","key":"pone.0253811.ref029","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jchromb.2010.02.004","article-title":"Identification and quantification of the glucose degradation product glucosone in peritoneal dialysis fluids by HPLC\/DAD\/MSMS","volume":"878","author":"S Mittelmaier","year":"2010","journal-title":"Journal of Chromatography B"},{"key":"pone.0253811.ref030","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/978-3-642-45993-1_8","volume-title":"Moderne Methoden der Pflanzenanalyse. Modern Methods of Plant Analysis","author":"E Stahl","year":"1962"},{"key":"pone.0253811.ref031","first-page":"1620","volume-title":"European Pharmacopoeia 10.0. Senna leaf","author":"Council of Europe","year":"2019"},{"key":"pone.0253811.ref032","first-page":"1631","volume-title":"European Pharmacopoeia 10.0. St John\u2019s wort","author":"Council of Europe","year":"2019"},{"key":"pone.0253811.ref033","first-page":"3408","volume-title":"European Pharmacopoeia 10.0. Ofloxacin","author":"Council of Europe","year":"2019"},{"key":"pone.0253811.ref034","author":"European Medicines Agency","year":"2006","journal-title":"ICH Q3A (R2) Impurities in new drug substances"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0322667","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T18:25:32Z","timestamp":1625250332000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253811"}},"subtitle":[],"editor":[{"given":"A. M.","family":"Abd El-Aty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253811","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0322667","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]}}}