Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Pharmaceutics Année : 2022

Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation.

Résumé

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.
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hal-04160174 , version 1 (12-07-2023)

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Heloise Henry, Jean-Francois Goossens, Mostafa Kouach, Damien Lannoy, David Seguy, et al.. Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation.. Pharmaceutics, 2022, Pharmaceutics, 14 (5), pp.1081. ⟨10.3390/pharmaceutics14051081⟩. ⟨hal-04160174⟩

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