Degradation of Epinephrine Induced by Bisulfite * *School of Pharmacy, University of Wisconsin, Madison, and Parke, Davis and Co., Detroit, Mich.

Schroeter, Louis C.; Higuchi, Takeru; Schuler, Edward E.

doi:10.1002/jps.3030471013

Cited by 29 publications

(4 citation statements)

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“…Metals, notably copper, iron, and zinc, destroy its activity. In solution with sulfite or bisulfite, it slowly forms an inactive sulfonate (17). The red color that forms when neutral or alkaline solutions are exposed to air is caused by adrenochrome.…”

Section: Stabilitymentioning

confidence: 99%

Epinephrine and Norepinephrine

Pugsley¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Epinephrine (E), norepinephrine (NE), and dopamine (DA) belong to a class of compounds known as catecholamines. A number of physical and chemical properties of E and NE, together with analytical techniques used to measure these amines and their metabolites, are reviewed. E was originally isolated from bovine adrenal glands; however, E and related compounds are now synthesized commercially from the starting material, catechol. The biosynthesis, storage, release, and the termination of action of catecholamines by re‐uptake into the presynaptic neuron that released the amine, plus mechanisms involved in regulating levels of amines in the nerve terminals, are reviewed. By virtue of functional and molecular biology studies, at least 15 subtypes of catecholamine receptors have been identified. In most cases, these physically distinct subtypes each have important second messengers and pharmacological consequences that are summarized. Catecholamines and related compounds exhibit a wide diversity of physiological functions, and thus are involved therapeutically in a wide range of uses both in the peripheral and central nervous system.

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Section: Stabilitymentioning

confidence: 99%

Epinephrine and Norepinephrine

Pugsley¹

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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“…Sodium bisulfite (SBS), used as a stabilizer in injectable preparations, is known to degrade various drugs including thiamine, 2) epinephrine, 3) gabexate mesilate, 4) nafamostat mesilate, 5) urokinase, 6) morphine 7) and fluorouracil. 8) However, there are no reports of detailed kinetic studies on the degradation of meropenem in the presence of SBS.…”

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confidence: 99%

Prediction of the Stability of Meropenem in Intravenous Mixtures

Takasu

Yoshida

Tange

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this study was to predict the stability of meropenem in a mixed infusion. The hydrolysis of meropenem in aqueous solution was found to be accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and L-cysteine. Equations were derived for the degradation rate constants (k obs ) of pH, SBS and L-cysteine, and fractional rate constants were estimated by the nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (E a ) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the characteristic pH curve. From these results, an equation was derived giving the residual ratio (%) of meropenem at any time after mixing an infusion containing SBS and/or L-cysteine at any temperature, and in the pH range 4.0-10.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).Key words stability prediction; meropenem; pH; sodium bisulfite (SBS); L-cysteine; degradation rate constant Carbapenems are the most potent β-lactam antibiotics and were first developed in the 1980s to enhance resistance to β-lactamases. The early carbapenems were not very hydrolytically stable, however, limiting drug administration to controlled intravenous infusions. In the search for a more stable compound with better toxicity profile, the basic nuclear structure was maintained and a dimethyl carbamoyl-pyrrolidinylthio group was added as a weakly basic C-2 side-chain. This resulted in a reduction of central toxicity and nephrotoxicity, while maintaining anti-pseudomonal activity. In addition, the improvement of stability (DHP-I stability) in vivo and the improvement of activity against Haemophilus influenzae, etc., were achieved by introducing 1-β-methyl group into the carbapenem frame, resulting in the creation of meropenem. The improvement in nephrotoxicity was the key advance in allowing the global development of meropenem as a single agent. 1)Meropenem is a broad-spectrum carbapenem, active against several clinically relevant Gram-positive and Gram-negative aerobes, anaerobic bacteria and Pseudomonas aeruginosa. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis through the inactivation of penicillin-binding proteins.Sodium and fluorouracil. 8) However, there are no reports of detailed kinetic studies on the degradation of meropenem in the presence of SBS.The prediction of the stability of a drug in an intravenous admixture (mixed infusion) is important for accurate and safe drug administration. Generally, the stability of a drug in a mixed infusion can be predicted from the pH profile and Arrhenius equation of the degradation rate constants, if the temperature and pH of the test solution are known. Although meropenem is generally administered as an infusion in saline, in some cases it may be mixed with other substances, such as amino acids. 9)A method for predicting the pH of mixed infusions was developed in orde...

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“…The degradation of (-)-epinephrine (1) in the presence of aqueous bisulfite or sulfite was first reported by Schroeter, Higuchi & Schuler (1958). They speculated that (+)-cpinine fl-sulfonate (2) is the reaction product.…”

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confidence: 99%