Leitzen Sarah, Vogel Matthias, Steffens Michael, Zapf Thomas, Müller Christa Elisabeth, Brandl Martin
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark.
Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany.
Pharmaceuticals (Basel). 2021 Nov 1;14(11):1121. doi: 10.3390/ph14111121.
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%, /) were autoclaved at 111 °C, 116 °C, and 121 °C 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 <0.078 μg/mL, and the limit of quantification was <0.236 μg/mL. The autoclaving time of 121 °C 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.
葡萄糖溶液的热灭菌会因氧化、水解和脱水导致各种葡萄糖降解产物（GDPs）的形成。由于其高反应性，GDPs在肠胃外给药后可能产生毒性作用。在本研究中，使用高效液相色谱 - 串联质谱法（LC - MS/MS）研究了F0概念在热灭菌过程中对特定时间/温度模型的应用及其对肠胃外葡萄糖溶液中GDPs形成的影响。将葡萄糖溶液（10%，/）在111℃、116℃和121℃下高压灭菌不同时间。在用邻苯二胺衍生化后，通过优化的LC - MS/MS方法对GDPs乙二醛、甲基乙二醛、葡糖酮、3 - 脱氧葡糖酮/3 - 脱氧半乳糖酮、3,4 - 二脱氧葡糖酮 - 3 - 烯和5 - 羟甲基糠醛进行定量。对于所有GDPs，检测限<0.078μg/mL，定量限<0.236μg/mL。121℃和15分钟的高压灭菌时间导致3 - DG/3 - DGal和5 - HMF的含量最低，但GO和2 - KDG的含量最高。所提出的LC - MS/MS方法快速且灵敏。到目前为止，只有5 - HMF的浓度受到监管当局的限制。我们的结果表明药典应重新考虑各种GDPs的杂质限度，特别是毒性更强的如GO和MGO。
