Monographs: Pharmaceutical substances: Deferoxamini mesilas - Deferoxamine mesilate

Molecular formula. C₂₅H₄₈N₆O₈,CH₄O₃S

Relative molecular mass, 656.8

Graphic formula.

Chemical name. N-[5-[3-[(5-Aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-(N-hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid monomethanesulfonate (salt); N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxyamino]pentyl]-N-(5-aminopentyl)-N-hydroxybutanediamide monomethanesulfonate (salt); CAS Reg. No. 138-14-7.

Other name. Desferrioxamine mesylate.

Description. A white to yellowish white powder; odourless or almost odourless.

Solubility. Soluble in 5 parts of water; soluble in ethanol (~750 g/l) TS; slightly soluble in methanol R; practically insoluble in ether R.

Category. Antidote to iron poisoning.

Storage. Deferoxamine mesilate should be kept in a well-closed container, protected from light, and stored at a temperature not exceeding 4 °C.

Requirements

Definition. Deferoxamine mesilate contains not less than 98.0% and not more than 102.0% of C₂₅H₄₈N₆O₈,CH₄O₃S, calculated with reference to the anhydrous substance.

Manufacture. The production method must be evaluated to determine the potential for formation of alkyl mesilates, which is particularly likely to occur if the reaction medium contains lower alcohols. Where necessary, the production method is validated to demonstrate that alkyl mesilates are not detectable in the final product.

Identity tests

A. Dissolve 5 mg in 5 ml of water, add 2 ml of trisodium orthophosphate (2 g/l) TS, mix, then add 1 ml of sodium 1,2-naphthoquinone-4-sulfonate (5 g/l) TS; a blackish brown colour is produced.

B. The titrated solution obtained in the assay is reddish brown in colour. To 5 ml of the titrated solution add 2 ml of benzyl alcohol R and shake; the colour is extracted. To a further 5 ml of the titrated solution add 2 ml of ether R and shake; the colour is not extracted.

Heavy metals. Use 1.0 g for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 3; determine the heavy metals content according to Method A; not more than 20 μg/g.

Chlorides. Dissolve 0.7 g in a mixture of 2 ml of nitric acid (~130 g/l) TS, and proceed as described under 2.2.1 Limit test for chlorides; the chloride content is not more than 0.35 mg/g.

Sulfates. Dissolve 0.85 g in 40 ml of water, and proceed as described under 2.2.2 Limit test for sulfates; the sulfate content is not more than 0.6 mg/g.

Clarity and colour of solution. A solution of 1.0 g in 10 ml of water is clear; measure the absorbance of the solution in a 1-cm layer at 420 nm; not more than 0.10.

Sulfated ash. Not more than 1.0 mg/g.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using about 1 g of the substance; the water content is not more than 20 mg/g.

pH value. pH of a 0.10 g/ml solution in carbon-dioxide-free water R, 3.5-6.0.

Assay. Dissolve about 0.3 g, accurately weighed, in 15 ml of water and add 2 ml of sulfuric acid (0.05 mol/l) VS. Titrate slowly with ferric ammonium sulfate (0.1 mol/l) VS, determining the end-point potentiometrically using a platinum electrode and a calomel reference electrode. Each ml of ferric ammonium sulfate (0.1 mol/l) VS is equivalent to 65.68 mg of C₂₅H₄₈N₆O₈,CH₄O₃S. (Keep the titrated solution for identity test B.)