Ficts and facts of epinephrine and norepinephrine stability in injectable solutions

Hoellein, Ludwig; Holzgrabe, Ulrike

doi:10.1016/j.ijpharm.2012.05.017

Cited by 46 publications

(45 citation statements)

References 22 publications

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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%

“…Catecholamines degrade rapidly via oxidative reactions which are catalyzed by oxygen, pH > 6, heavy metal ions, heat and UV-Vis. Well known degradation products are adrenochrome and noradrenochrome [4,5]. However, there are no acceptance limits defined for the content of degradation products in the relevant monographies of the Ph.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, temperature and the extent of light exposure are to be considered during storage and use of the medicinal products. A review of stability studies regarding E and NE injection solutions and the influence of dilution and concentration of excipients was recently published by Hoellein et al [5]. The objective of our study was to evaluate the physicochemical stability of RTA and RTU preparations containing E and NE in standardized concentrations and prepared batch wise in the Pharmacy Department of the University Medical Center Mainz as basis for assigning shelf-lives.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Hplc Assay and Physicochemical Stabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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“…Quantitative Determination of Adrenaline in the Irrigating Solution 12) The HPLC system (LC-10 AT; Shimadzu, Kyoto, Japan) was connected with an electrochemical detector (ECD-100; EICOM, Kyoto, Japan) using a C 18 reverse-phase column (5 µm, 150×3.0 mm, EICOM). The mobile phase consisted of citrate-acetate buffer, 4% octane-sulfonic acid, and 0.05% disodium ethylenediaminetetraacetic acid (EDTA), in 15% methanol, pH 2.8, and was pumped at a rate of 0.5 mL/ min.…”

Section: Reagentsmentioning

confidence: 99%

Stability of Adrenaline in Irrigating Solution for Intraocular Surgery

Shibata

Kimura

Taogoshi

et al. 2016

Biological & Pharmaceutical Bulletin

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Intraocular irrigating solution containing 1 µg/mL adrenaline is widely used during cataract surgery to maintain pupil dilation. Prepared intraocular irrigating solutions are recommended for use within 6 h. After the irrigating solution is admistered for dilution, the adrenaline may become oxidized, and this may result in a decrease in its biological activity. However, the stability of adrenaline in intraocular irrigating solution is not fully understood. The aim of this study was to evaluate the stability of adrenaline in clinically used irrigating solutions of varying pH. Six hours after mixing, the adrenaline percentages remaining were 90.6% 3.7 (pH 7.2), 91.1% 2.2 (pH 7.5), and 65.2% 2.8 (pH 8.0) of the initial concentration. One hour after mixing, the percentages remaining were 97.6% 2.0 (pH 7.2), 97.4% 2.7 (pH 7.5), and 95.6% 3.3 (pH 8.0). The degradation was especially remarkable and time dependent in the solution at pH 8.0. These results indicate that the concentration of adrenaline is decreased after preparation. Moreover, we investigated the influence of sodium bisulfite on adrenaline stability in irrigating solution. The percentage adrenaline remaining at 6 h after mixing in irrigating solution (pH 8.0) containing sodium bisulfite at 0.5 µg/mL (concentration in irrigating solution) or at 500 µg/mL (concentration in the undiluted adrenaline preparation) were 57.5 and 97.3%, respectively. Therefore, the low concentration of sodium bisulfite in the irrigating solution may be a cause of the adrenaline loss. In conclusion, intraocular irrigation solution with adrenaline should be prepared just prior to its use in surgery.

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“…and notoginsenoside R1, under acidic, alkaline, oxidative, thermal, ionic and irradiation conditions in aqueous solution as well as the stability of the five PNSs in XST injection solution itself (Karioti et al, 2011;Hoellein and Holzgrabe, 2012). The degradation kinetics of the five ingredients was determined and calculated in both the aqueous solution and the injection; moreover, the degradation mechanism was deduced.…”

Section: Introductionmentioning

confidence: 99%

Compatible stability study of panax notoginseng saponin injection (xueshuantong®) in combination with 47 different injectables

Wang

Zhang

Dong

et al. 2016

Biomedical Chromatography

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Panax Notoginseng Saponin (PNS) injection (Xueshuantong®, XST) plays an important role in acute and chronic treatment of cardiovascular disease in China. XST, a freeze-dried powder injection of PNS, contains ginsenosides, Rg1, Rb1, Re, Rd. and notoginsenoside, R1. Study of the stability of herbal medicine injections is limited. The degradation products may contribute to adverse drug reactions (ADRs). The stability kinetics and degradation mechanisms of the five ingredients of PNS in XST injection were systematically explored in aqueous solution. The compatible stability of XST injection in combination with 47 injectables was evaluated using biophysical analysis. A principal components analysis model provided a good clustering result after compatibility. The degradation of the five ingredients in aqueous solution was found to be acid, temperature, oxidation and trivalent ion-dependent. All ingredients were much more stable in XST injection than in aqueous solutions. Nine degradation products were identified by adopting LC-Q-TOF/MS. Standards exceeding the osmotic pressure and/or particle size were found to be the probable causes of the ADR, which were related to drug combination. To minimize the risk of ADRs, drug combinations should be avoided until the complicated chemical matrices of the Chinese medicine injections are more clearly understood. Copyright © 2016 John Wiley & Sons, Ltd.

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Ficts and facts of epinephrine and norepinephrine stability in injectable solutions

Cited by 46 publications

References 22 publications

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

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

Stability of Adrenaline in Irrigating Solution for Intraocular Surgery

Compatible stability study of panax notoginseng saponin injection (xueshuantong®) in combination with 47 different injectables

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