Parenteral-nutrition (PN)-induced hyperglycemia increases morbidity and mortality and must be treated with insulin. Unfortunately, the addition of insulin to a ternary PN admixture leads to a rapid decrease in insulin content. Our study’s objective was to determine the mechanistic basis of insulin’s disappearance. The literature data suggested the presence of a glycation reaction; we therefore validated an LC-MS/MS assay for insulin and glycated insulin. In a 24-h stability study, 20 IU/L of insulin was added to a binary PN admixture at pH 3.6 or 6.3. When the samples were diluted before analysis with a near-neutral diluent, insulin was fully stable at pH 3.6, while a loss of around 50% was observed at pH 6.3. Its disappearance was shown to be inversely correlated with the appearance of monoglycated insulin (probably a Schiff base adduct). Monoglycated insulin might also undergo a back-reaction to form insulin after acidic dilution. Furthermore, a second monoglycated insulin species appeared in the PN admixture after more than 24 h at high temperature (40 °C) and a high insulin concentration (1000 IU/L). It was stable at acidic pH and might be an Amadori product. The impact of insulin glycation under non-forced conditions on insulin’s bioactivity requires further investigation.

中文翻译：

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常规胰岛素在肠外营养混合物中的行为：LC/MS-MS 测定的验证和胰岛素糖基化的体外评价

肠外营养 (PN) 引起的高血糖会增加发病率和死亡率，必须用胰岛素治疗。不幸的是，在三元 PN 混合物中添加胰岛素会导致胰岛素含量迅速下降。我们研究的目的是确定胰岛素消失的机制基础。文献数据表明存在糖化反应；因此，我们验证了胰岛素和糖化胰岛素的 LC-MS/MS 测定。在一项 24 小时稳定性研究中，将 20 IU/L 的胰岛素添加到 pH 3.6 或 6.3 的二元 PN 混合物中。当样品在分析前用近中性稀释剂稀释时，胰岛素在 pH 3.6 时完全稳定，而在 pH 6.3 时观察到大约 50% 的损失。它的消失与单糖化胰岛素（可能是席夫碱加合物）的出现呈负相关。单糖化胰岛素也可能在酸性稀释后发生逆反应形成胰岛素。此外，在高温（40°C）和高胰岛素浓度（1000 IU/L）下超过 24 小时后，PN 混合物中出现了第二种单糖化胰岛素种类。它在酸性 pH 值下稳定，可能是 Amadori 产品。非强制条件下胰岛素糖基化对胰岛素生物活性的影响需要进一步研究。