葡萄糖溶液的热灭菌可导致由于氧化而形成各种葡萄糖降解产物(GDPs),水解,和脱水。由于其高反应性,GDP在肠胃外施用后可具有毒性作用。在这项研究中,使用高效液相色谱-串联质谱(LC-MS/MS)研究了F0概念在热灭菌过程中修改特定时间/温度模型及其对胃肠外葡萄糖溶液中GDPs形成的影响。葡萄糖溶液(10%,w/v)在111℃高压灭菌,116°C,和121°C不同的持续时间。GDPs乙二醛,甲基乙二醛,葡萄糖酮,3-脱氧葡萄糖酮/3-脱氧半乳糖酮,3,4-二脱氧葡糖酮-3-烯,和5-羟甲基糠醛在用邻苯二胺衍生化后通过优化的LC-MS/MS方法定量。对于所有的GDP,检测限<0.078μg/mL,定量限<0.236μg/mL。121°C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。但在最高水平的GO和2-KDG。所提出的LC-MS/MS方法快速、灵敏。到目前为止,只有5-HMF浓度受到监管机构的限制。我们的结果表明重新考虑各种GDP的杂质限制,尤其是更有毒的,如GO和MGO,根据药典。
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 °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.