Stability of Ready-to-Administer and Ready-to-Use Epinephrine and Norepinephrine Injection Solutions

Heeb, Rita Marina; Stollhof, Bettina; Reichhold, Julia; Thiesen, Judith; Krämer, Irene

doi:10.1515/pthp-2017-0024

Cited by 5 publications

(10 citation statements)

References 4 publications

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“…The sensitivity of catecholamine degradation to light has previously been shown,15 27 but it could not be responsible for the NE degradation in our study because each container tested was stored in a closed enclosure. Other studies have assumed that the major determinant of the degradation process is pH 16.…”

Section: Discussionmentioning

confidence: 62%

“…The long-term stability of 0.2 and 0.5 mg/mL NE solutions diluted in NS in PP syringes and ready-to-use-COC vials had not been investigated before. The closest in terms of study design assessed the stability of 0.1, 0.2, 0.4 and 0.04 mg/mL NE solutions in amber glass vials, and 0.01 mg/mL NE solutions diluted in D5W stored in 10 mL PP syringes for 12 months at +2°C to 8°C and ambient temperature 15. Results were partly comparable with ours as the stability of 0.1, 0.2 and 0.4 mg/mL solutions was maintained over the study period when stored refrigerated.…”

Section: Discussionmentioning

confidence: 99%

“…The degradation pathways of catecholamines via their oxidative reaction responsible for colouring have been widely described 24. Oxidation leads to the formation of noradrenochromes15 which account for the greyish-brown colour. This oxidative process is catalysed by oxygen, heat, alkalinisation with a pH value >6, heavy metal ions, and exposure to UV or daylight 14 16 17.…”

Section: Discussionmentioning

confidence: 99%

“…The safety and efficacy of COC vials to maintain the long-term stability of injectable solutions have previously been demonstrated 18. The counting of sub-visible particles is another strong point, as this was not performed in previous stability studies 8–13 15–17…”

Section: Discussionmentioning

confidence: 99%

“…Compounding in hospital pharmacies provides qualitative injectable solutions and avoids the dilution step in the ward 6. The stability of NE is known to be highly sensitive to storage conditions7 and the 365 day stability of 0.2 mg/mL and 0.5 mg/mL solutions of NE diluted in NS and stored in polypropylene (PP) syringes or cyclic olefin copolymer (COC) vials has never been assessed before 8–17…”

Section: Introductionmentioning

confidence: 99%

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Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL

et al. 2020

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Objectives Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes. Methods A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at −20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure. results Stability was successfully maintained for every concentration and container tested when stored at −20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature. Conclusions Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL

et al. 2020

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Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Resmi,

Parvathy,

Anjali

et al. 2024

ChemistrySelect

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A review of recent literature reveals a spurt in the publications using alginate dialdehyde (ADA)‐based hydrogels. This study evaluates the stability and characteristics of ADA solutions stored at different temperatures (4 & −20 °C; designated as ADA4°C & ADA−20°C) and durations (1, 3, and 6 months), and gives valuable insights into the shelf life, a parameter important in a clinical setting. ADA solutions were characterized for their viscosity, aldehyde content, molecular weight, and chemical structure before and after storage. The solution viscosities of ADA4°C showed a decreasing trend over 6 months while that of ADA‐20°C showed an increase. Compared to freshly prepared ADA, a significant reduction in aldehyde content, from 40.1±1.4 % to 37.1±1.01 %, was observed for ADA4°C stored for 6 months, but the aldehyde content was stable for ADA−20°C stored for the same period. Molecular weight remained stable (~6800 g/mol) irrespective of the storage temperatures. Injectable hydrogels were prepared by reacting the stored ADA solutions with 20 % aqueous solutions of gelatin. Hydrogels prepared with ADA stored at 4 °C for 6 months showed a significant increase in gelation time from 4.3±1.5 to 8.79±0.1 min and a decrease in degree of crosslinking from 54.3±1.4 % to 29.2±2.3 %. A decreasing trend was observed for properties such as water uptake (from 470 to 961 %) and tensile strength (from 348 to 282 kPa). Hydrogels made with ADA−20°C demonstrated better retention of physicochemical properties over time. In vitro studies revealed that the hydrogels showed a non‐cytotoxic response towards L929 cells irrespective of the storage conditions. LIVE/DEAD assay and F‐Actin staining revealed good cell proliferation on the hydrogels. In conclusion, retention of the properties of ADA in its aqueous solution requires careful control of storage temperatures.

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Effects of long-term norepinephrine treatment on normal immortalized ovarian and fallopian tube cells

Dash

Yoder

Mesa

et al. 2021

Sci Rep

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Sustained adrenergic stimulation by norepinephrine (NE) contributes to ovarian carcinoma metastasis and impairment of chemotherapy response. Although the effect of sustained NE stimulation in cancer progression is well established, less is known about its role in cancer initiation. To determine the extent to which stress hormones influence ovarian cancer initiation, we conducted a long-term (> 3 months; > 40 population doublings) experiment in which normal immortalized fallopian tube secretory (iFTSEC283) and ovarian surface epithelial (iOSE11) cell lines and their isogenic pairs containing a p53 mutation (iFTSEC283p53R175H; iOSE11p53R175H), were continuously exposed to NE (100 nM, 1 μM, 10 μM). Fallopian tube cells displayed a p53-independent increase in proliferation and colony-forming ability in response to NE, while ovarian surface epithelial cells displayed a p53-independent decrease in both assays. Fallopian tube cells with mutant p53 showed a mild loss of chromosomes and TP53 status was also a defining factor in transcriptional response of fallopian tube cells to long-term NE treatment.

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Stability of Ready-to-Administer and Ready-to-Use Epinephrine and Norepinephrine Injection Solutions

Cited by 5 publications

References 4 publications

Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL

Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL

Implications of Storage Conditions on the Characteristics of Alginate Dialdehyde and Its Hydrogels

Effects of long-term norepinephrine treatment on normal immortalized ovarian and fallopian tube cells

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