Stability of Norepinephrine Solutions in Normal Saline and 5% Dextrose in Water

Walker, Scott; Law, Shirley; Garland, Jill; Fung, Esther; Iazzetta, John

doi:10.4212/cjhp.v63i2.896

Cited by 12 publications

(18 citation statements)

References 14 publications

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“…However, NE injection solutions, 0.01 mg/mL in 10 mL PP syringes, were seen to be stable for only 6 months when stored refrigerated and 28 days when stored at ambient temperature. Previous studies successfully assessed the stability of NE solutions over shorter periods,9–14 with storage at ambient9 11–13 or refrigerated9 14 temperatures, in polyvinyl chloride bags,9 11 13 14 PP syringes,12 with dilution in NS9 11 or D5W,9 11–14 exposed to9 11 12 or protected from9 12–14 light, with different NE concentrations. The NE commercial solution used for our stability assay was devoid of antioxidative stabilising agents.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, many converging arguments have forced us to assume that temperature plays a major role in catalysing the degradation process of NE, as sub-visible particulate contamination was low when stored in frozen and refrigerated conditions while solutions stored at ambient temperature became coloured. The assumption that stability is prolonged with refrigerated or frozen storage has already been raised,9 10 and many studies have successfully used freezing to lengthen drug stability. Protocols using microwaves for defrosting have also been published.…”

Section: Discussionmentioning

confidence: 99%

“…A reversed-phase fast liquid chromatography (FLC) system (Agilent 1260 Infinity LC, Les Ulis, France) equipped with an Apollo C18 Alltech column (5 µm, 250 mm × 4.6 mm, Grace, Epernon, France) maintained at +25°C coupled with an ultra-violet (UV) detector (1260 MWD DEAAZ00942) was used to measure NE concentrations. The wavelength was set at 279 nm 9. The injection volume was 5 µL for all analyses.…”

Section: Methodsmentioning

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: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

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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“…Variations of the HPLC assays are used for stability testing of diluted E and NE injection solutions [5,13,14]. Based on the known methods [10,11] we established an HPLC assay for quantitative analysis of NE using the µBondapak C18 column and SDS containing mobile phase.…”

Section: Hplc Assay and Physicochemical Stabilitymentioning

confidence: 99%

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

Heeb

Stollhof

Reichhold

et al. 2017

Pharmaceutical Technology in Hospital Pharmacy

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AbstractBackgroundIn the University Medical Centre Mainz, standard concentrations are defined for medicinal products to be administered by continuous injection with syringe pumps in adult intensive care patients. The objective of this study was to evaluate the physicochemical stability of ready-to-use and ready-to-administer preparations containing Epinephrine (E) and Norepinephrine (NE) in standardized concentrations and prepared batch wise in the pharmacy department as basis for assigning shelf-lives.MethodsE 20 µg/mL and NE 10 µg/mL in disposable syringes and NE 40, 100, 200, 400 µg/ml in 50 ml amber type I glass vials were prepared batch wise and the concentrations were analyzed by stability-indicating, validated reversed-phase HPLC-PDA assays. Test solutions for long-term stability studies were stored under refrigeration (2–8 °C) for 6–12 months or at elevated temperatures (21–27 °C) light protected for up to 6 months or without light protection for up to one month. Osmolality and pH were measured on predefined intervals.ResultsThe concentrations of E in 50 mL syringes and NE in 10 mL syringes remained unchanged over a period of 6 months when stored at 2–8 °C. NE preparations of different concentrations prepared in amber glass vials remained stable over a study period of 12 months. At RT the shelf-life decreased to about 6 months and the exposure to mixed daylight at RT caused loss of stability in only few days.ConclusionsBatch wise preparation of ready-to-administer (RTA) preparations containing 20 µg/mL E or 10 µg/mL NE in disposable syringes as well as ready-to-use (RTU) preparations containing 40, 100, 200 and 400 µg/mL NE was successfully implemented in a pharmacy department. Storage of the preparations at refrigerated temperatures is required to obtain acceptable shelf-lives of 6–12 months. Elevated temperatures and especially exposure to mixed daylight significantly decreased the shelf life.

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Culture-directed antibiotics in peritoneal dialysis solutions: a systematic review focused on stability and compatibility

Ling,

Sud,

Patel

et al. 2023

J Nephrol

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Background This systematic review summarises the stability of less commonly prescribed antibiotics in different peritoneal dialysis solutions that could be used for culture-directed therapy of peritonitis, which would be especially useful in regions with a high prevalence of multidrug antibiotic-resistant strains. Methods A literature search of Medline, Scopus, Embase and Google Scholar for articles published from inception to 25 January, 2023 was conducted. Only antibiotic stability studies conducted in vitro and not recently reviewed by So et al. were included. The main outcomes were chemical, physical, antimicrobial and microbial stability. This protocol was registered in PROSPERO (registration number CRD42023393366). Results We screened 1254 abstracts, and 28 articles were included in the study. In addition to those discussed in a recent systematic review (So et al., Clin Kidney J 15(6):1071–1078, 2022), we identified 18 antimicrobial agents. Of these, 9 have intraperitoneal dosing recommendations in the recent International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines, and 7 of the 9 had stability data applicable to clinical practice. They were cefotaxime, ceftriaxone, daptomycin, ofloxacin, and teicoplanin in glucose-based solutions, tobramycin in Extraneal solution only and fosfomycin in Extraneal, Nutrineal, Physioneal 1.36% and 2.27% glucose solutions. Conclusions Physicochemical stability has not been demonstrated for all antibiotics with intraperitoneal dosing recommendations in the ISPD peritonitis guidelines. Further studies are required to determine the stability of antibiotics, especially in icodextrin-based and low-glucose degradation products, pH-neutral solutions. Graphical abstract

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Stability of Norepinephrine Solutions in Normal Saline and 5% Dextrose in Water

Abstract: Background: Most previous stability studies for norepinephrine have reported the percentage of drug remaining in IV solutions after only 24 h. No previously published study has evaluated the effect of light on the stability of this drug.

Cited by 12 publications

References 14 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

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

Culture-directed antibiotics in peritoneal dialysis solutions: a systematic review focused on stability and compatibility

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