Glucose solutions are commonly heated before use in medical and biotech applications to maintain cleanliness, however the resulting degradants can be toxic. This study examines two approaches to evaluating the heat degradants resulting from holding a 40% glucose solution at 55°C for 5 weeks: first, chemical changes to the solution were identified and quantified via analytical testing, and second the toxicity of the heat‐degraded 40% glucose solution was evaluated empirically by using it as a feed stock for a fed‐batch CHO‐cell‐based protein therapeutic manufacturing process. Colorimetric analysis quantified a color change during heating, and liquid chromatography assays measured an increase in the concentrations of two unknown degradants along with the commonly identified glucose impurity 5‐hydroxymethylfurfural (5‐HMF). Solution pH decreased over time, corresponding with an increase in formic acid concentration as measured via GC–MS. Despite this, cell culture toxicity was not observed, and protein productivity and product quality were maintained.

中文翻译：

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分析葡萄糖热降解物并评估其对CHO细胞培养过程影响的多方面方法

葡萄糖溶液通常在用于医疗和生物技术应用之前先进行加热，以保持清洁度，但是所产生的降解物可能是有毒的。这项研究研究了两种评估热降解剂的方法，这些方法是将40％葡萄糖溶液在55°C下放置5周而产生的：第一，通过分析测试确定并量化溶液的化学变化，第二，热降解的毒性通过将其用作基于补料分批CHO细胞的蛋白质治疗生产过程的原料，对40％葡萄糖溶液进行了经验评估。比色分析量化了加热过程中的颜色变化，液相色谱分析法测量了两种未知降解物的浓度以及常见的葡萄糖杂质5-羟甲基糠醛（5-HMF）的增加。溶液的pH值随时间下降，这与通过GC-MS测定的甲酸浓度增加相对应。尽管如此，仍未观察到细胞培养毒性，并且蛋白质生产率和产品质量得以维持。