Effect of pH, chlorobutanol, cysteine hydrochloride, ethylenediaminetetraacetic acid, propylene glycol, sodium metabisulfite, and sodium sulfite on furosemide stability in aqueous solutions. 1980

K A Shah, and V Das Gupta, and K R Stewart

A study was conducted to determine the effects of pH, two antioxidants, a chelating agent, a preservative, and propylene glycol on furosemide stability. Aqueous solutions of furosemide containing 10% alcohol (v/v) were prepared in phosphate buffers with various pH values (5, 6, and 9) whose ionic strength was adjusted to 0.1 M with potassium chloride. Some solutions contained chlorobutanol, ethylenediaminetetraacetic acid, or sodium metabisulfite. Another set of aqueous solutions contained phosphate buffer (0.1 M), alcohol (10% v/v), and propylene glycol (40% v/v) with or without cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite. The solutions were divided into two parts, stored at 24 and 50 degrees, and assayed frequently using a previously developed high-pressure liquid chromatographic procedure. At the lowest pH value (pH 5), furosemide appeared to be very unstable. Cysteine hydrochloride, ethylenediaminetetraacetic acid, and sodium sulfite failed to improve the stability of furosemide. Chlorobutanol and sodium metabisulfite had an adverse effect on the stability, probably due to the fact that they decreased the pH of the solution. The pH value appears to be the only critical factor for the stability of furosemide. Buffered solutions containing propylene glycol were very stable at both temperatures for 170 days, and they tasted good.

UI MeSH Term Description Entries
D011409 Propylene Glycols Derivatives of propylene glycol (1,2-propanediol). They are used as humectants and solvents in pharmaceutical preparations. Propanediols,Glycols, Propylene
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D002724 Chlorobutanol A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics. Acetonchloroform,Chlorbutol,Trichlorbutanol,Chloretone,Chlorobutanol, Anhydrous,Anhydrous Chlorobutanol
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004492 Edetic Acid A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. EDTA,Edathamil,Edetates,Ethylenediaminetetraacetic Acid,Tetracemate,Calcium Disodium Edetate,Calcium Disodium Versenate,Calcium Tetacine,Chelaton 3,Chromium EDTA,Copper EDTA,Coprin,Dicobalt EDTA,Disodium Calcitetracemate,Disodium EDTA,Disodium Ethylene Dinitrilotetraacetate,Distannous EDTA,Edetate Disodium Calcium,Edetic Acid, Calcium Salt,Edetic Acid, Calcium, Sodium Salt,Edetic Acid, Chromium Salt,Edetic Acid, Dipotassium Salt,Edetic Acid, Disodium Salt,Edetic Acid, Disodium Salt, Dihydrate,Edetic Acid, Disodium, Magnesium Salt,Edetic Acid, Disodium, Monopotassium Salt,Edetic Acid, Magnesium Salt,Edetic Acid, Monopotassium Salt,Edetic Acid, Monosodium Salt,Edetic Acid, Potassium Salt,Edetic Acid, Sodium Salt,Ethylene Dinitrilotetraacetate,Ethylenedinitrilotetraacetic Acid,Gallium EDTA,Magnesium Disodium EDTA,N,N'-1,2-Ethanediylbis(N-(carboxymethyl)glycine),Potassium EDTA,Stannous EDTA,Versenate,Versene,Acid, Edetic,Acid, Ethylenediaminetetraacetic,Acid, Ethylenedinitrilotetraacetic,Calcitetracemate, Disodium,Dinitrilotetraacetate, Disodium Ethylene,Dinitrilotetraacetate, Ethylene,Disodium Versenate, Calcium,EDTA, Chromium,EDTA, Copper,EDTA, Dicobalt,EDTA, Disodium,EDTA, Distannous,EDTA, Gallium,EDTA, Magnesium Disodium,EDTA, Potassium,EDTA, Stannous,Edetate, Calcium Disodium,Ethylene Dinitrilotetraacetate, Disodium,Tetacine, Calcium,Versenate, Calcium Disodium
D005665 Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY. Frusemide,Fursemide,Errolon,Frusemid,Furanthril,Furantral,Furosemide Monohydrochloride,Furosemide Monosodium Salt,Fusid,Lasix
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D013447 Sulfites Inorganic salts of sulfurous acid. Sulfite,Sulfites, Inorganic,Inorganic Sulfites

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