{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:27:45Z","timestamp":1791462465139,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time\/temperature models during heat sterilization and their influence on the formation of GDPs in parenteral glucose solutions was investigated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS\/MS). Glucose solutions (10%, w\/v) were autoclaved at 111 \u00b0C, 116 \u00b0C, and 121 \u00b0C for different durations. The GDPs glyoxal, methylglyoxal, glucosone, 3-deoxyglucosone\/3-deoxygalactosone, 3,4-dideoxyglucosone-3-ene, and 5-hydroxymethylfurfural were quantified after derivatization with o-phenylenediamine by an optimized LC-MS\/MS method. For all GDPs, the limit of detection was &lt;0.078 \u03bcg\/mL, and the limit of quantification was &lt;0.236 \u03bcg\/mL. The autoclaving time of 121 \u00b0C and 15 min resulted in the lowest levels of 3-DG\/3-DGal and 5-HMF, but in the highest levels of GO and 2-KDG. The proposed LC-MS\/MS method is rapid and sensitive. So far, only 5-HMF concentrations are limited by the regulatory authorities. Our results suggest reconsidering the impurity limits of various GDPs, especially the more toxic ones such as GO and MGO, by the Pharmacopoeias.<\/jats:p>","DOI":"10.3390\/ph14111121","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:24:22Z","timestamp":1635805462000},"page":"1121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Quantification of Degradation Products Formed during Heat Sterilization of Glucose Solutions by LC-MS\/MS: Impact of Autoclaving Temperature and Duration on Degradation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-4168","authenticated-orcid":false,"given":"Sarah","family":"Leitzen","sequence":"first","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark"},{"name":"Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-3900","authenticated-orcid":false,"given":"Matthias","family":"Vogel","sequence":"additional","affiliation":[{"name":"Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Steffens","sequence":"additional","affiliation":[{"name":"Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Zapf","sequence":"additional","affiliation":[{"name":"Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0013-6624","authenticated-orcid":false,"given":"Christa Elisabeth","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn, 53121 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Brandl","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11932","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":"Haybrard","year":"2017","journal-title":"Sci. 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