Edetic acid

• BPEdetic Acid
• Ph. Eur.Edetic Acid
• USP–NFEdetic Acid

EDTA; acidum edeticum; ethylenediaminetetraacetic acid; (ethylenedinitrilo)tetraacetic acid; Versene Acid

N,N′-1,2-Ethanediylbis[N-(carboxymethyl)glycine] · [60-00-4]

UNII 9G34HU7RV0 · PubChem CID 6049

C10H16N2O8 · 292.24

Antioxidant, chelating agent

Typical concentrations: — · Dosage forms: Liquid, Semi-solid, Sterile (parenteral/ophthalmic)

A chelating (sequestering) agent used to bind trace metal ions that catalyse oxidation and other degradation reactions, typically at 0.005–0.1% w/v. It acts as an antioxidant synergist and enhances the activity of preservatives such as benzalkonium chloride against Gram-negative bacteria, particularly Pseudomonas. Because the free acid is poorly soluble, the more soluble disodium salt is usually preferred in aqueous products.

A white or almost white, odourless crystalline powder or colourless crystals.

pKa

about 2.0, 2.7, 6.2 and 10.3 (25 °C)

Melting point

decomposes on heating, above about 220 °C

Solubility

very slightly soluble in water; practically insoluble in ethanol and common organic solvents; dissolves in dilute alkali hydroxide solutions with salt formation

Chelation

forms stable, water-soluble 1:1 complexes with most di- and trivalent metal ions

Stable as the solid. Store in a well-closed container in a cool, dry place.

Incompatible with strong oxidising agents and strong bases. It complexes polyvalent metal ions and so is incompatible with metal-containing drugs and additives, and with metals such as copper, nickel and copper alloys.

Usually made by reacting ethylenediamine with formaldehyde and sodium cyanide under alkaline conditions to give tetrasodium edetate; acidification of the solution precipitates the free acid.

Poorly absorbed from the gastrointestinal tract and of low toxicity at the levels used as an excipient. Large doses chelate calcium and can cause hypocalcaemia, and edetates may cause mild irritation of the skin, eyes and mucous membranes; edetate-containing nebuliser solutions have been associated with bronchoconstriction. JECFA has set an ADI of 0–2.5 mg/kg body weight, expressed as calcium disodium edetate.

Observe normal precautions for the quantity handled. The powder may irritate the eyes, skin and respiratory tract; eye protection, gloves and a dust mask are recommended.

Included in the FDA Inactive Ingredient Database (non-parenteral preparations) and in non-parenteral medicines licensed in Europe. The salt calcium disodium edetate, rather than the free acid, is the form permitted as a food additive in Europe (E385).

Disodium edetate; calcium disodium edetate; tetrasodium edetate; trisodium edetate.

When edetic acid itself is used, it is commonly dissolved by adding an alkali to form a salt in situ. Its value as a preservative enhancer comes from removing calcium and magnesium from the outer membrane of Gram-negative bacteria, which makes them more permeable to the preservative.