Quantitative analysis of insulin in total parenteral nutrition bag in Taiwan

Abstract

Regular insulin can reduce hyperglycemia when directly added to total parenteral nutrition (TPN) solutions. Insulin is not routinely added to all TPN solutions. For patients who require insulin prior to the initiation of TPN supplement, one-third to one-half of the usual total daily dose can be added to the TPN bag as regular human insulin. However, an incorrect dose or an interaction between insulin and the TPN bag material may affect blood sugar control in clinical practice. Therefore, it is important to quantitatively determine the final dose of insulin in the TPN bag. High performance liquid chromatography is a very powerful technique for determining the purity of proteins. The goal of this study was to use high-performance liquid chromatography to perform quantitative analysis of insulin in a TPN bag. The analysis was performed under different light conditions (UV, fluorescent, and darkness) and different temperatures (25°C and 2-8°C). The results show that adsorption of insulin on an ethylene vinyl acetate TPN bag is significantly higher than that on glass. Based on the results, it is evident that regular insulin should be administered separately from TPN to reduce cost and eliminate wasteful disposal of TPN solutions.

Insulin Instability in Parenteral Nutrition Admixtures

“…Previous studies highlighted several potential causes of insulin loss. In some studies, for instance, lower concentrations of aromatic amino acids reduced insulin availability, trace elements and vitamins increased its recovery, ILE and the type of containers were responsible for insulin shift . Although we did not test our EVA bags, we believe that biosynthetic human recombinant short‐acting insulin loss occurred because of adherence to PN bag walls and filling tubes.…”

“…Quantity of triglycerides adherent to EVA surfaces steadily increased with emulsion exposure time, as proven by gravimetric measurements. Very recently, Yu et al confirmed that EVA bags are chemically active and attract insulin. Concurrently or alternatively, the chemical receptor points may also be saturated by insulin itself, which would explain why insulin recovery was greater in admixtures containing higher initial insulin dosages.…”

“…In terms of methodology, high‐performance liquid chromatography (HPLC)‐tandem mass spectrometry and HPLC itself are fast methods for analyzing insulin in aqueous solutions and pharmaceutical preparations, but they require a complex extraction procedure from organic lipid matrices, like PN admixtures. In this study, we thus chose to evaluate biosynthetic human recombinant short‐acting insulin stability by means of a high‐resolution immunometric method, which allows analyzing insulin on undiluted samples of PN admixtures .…”

“…The common sense approach to patients with PN‐associated hyperglycemia requires appropriate carbohydrate dosing, as well as the use of intravenous (IV) or subcutaneous insulin therapy . As the literature shows, the initial insulin dose does not remain entirely available when added to admixtures because it gets attached to bags and tubes . Insulin molecules seem to be very sensitive to changes in physical pressure exerted by an automated compounding device, temperature, and PN composition (types of amino acids, presence of intravenous lipid emulsion [ILE]).…”

“…Insulin molecules seem to be very sensitive to changes in physical pressure exerted by an automated compounding device, temperature, and PN composition (types of amino acids, presence of intravenous lipid emulsion [ILE]). They also seem to be electrostatically attracted and deactivated by PN's ethyl‐vinyl‐acetate (EVA) plastic bags and automated compounding device . In several of our departments, additional insulin had unexpectedly been infused in a syringe driver, separate to PN, to control glucose levels in stable patients without a convincing explanation.…”