Monographs: Pharmaceutical substances: Ergometrini hydrogenomaleas - Ergometrine hydrogen maleate

Molecular formula. C19H23N3O2,C4H4O4 or C23H27N3O6

Relative molecular mass. 441.5

Graphic formula.

Chemical name. 9,10-Didehydro-N-[(S)-2-hydroxy-1-methylethyl]-6-methylergoline-8β-carboxamide maleate (1:1) (salt); 9,10-didehydro-N-[(S)-2-hydroxy-1-methylethyl]-6-methylergoline-8β-carboxamide (Z)-2-butanedioate (1:1) salt; CAS Reg. No. 129-51-1.

Description. A white or faintly yellow, crystalline powder; odourless.

Solubility. Sparingly soluble in water and ethanol (~750 g/l) TS; practically insoluble in ether R.

Category. Oxytocic.

Storage. Ergometrine hydrogen maleate should be kept in a hermetically closed container, preferably in an inert atmosphere, such as nitrogen, protected from light and stored at a temperature between 2° and 8°C.

Additional information. Ergometrine hydrogen maleate darkens in colour on exposure to light. Even in the absence of light, Ergometrine hydrogen maleate is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures.

Requirements

Definition. Ergometrine hydrogen maleate contains not less than 98.0% and not more than 101.0% of C19H23N3O2,C4H4O4 calculated with reference to the dried substance.

Identity tests

A. Dissolve 15 mg in 5 ml of water; a blue fluorescence is produced.

B. See the test described below under "Related alkaloids". The principal spot obtained with solution B corresponds in position, appearance, and intensity with that obtained with solution C.

C. Dissolve 2 mg in 20 ml of water; to 1 ml of this solution add 2 ml of 4-dimethylaminobenzaldehyde TS1 and allow to stand for about 5 minutes; a deep blue colour is produced.

D. Dissolve 2 mg in 1 ml of water, and add 1 drop of bromine TS1; the colour of the reagent is discharged.

Specific optical rotation. Use a 10 mg/ml solution and calculate with reference to the dried substance; = +50° to +56°.

Clarity and colour of solution. A solution of 0.10 g in 10 ml of carbon-dioxide-free water R is clear and not more intensely coloured than standard colour Yw3 when compared as described under 1.11 Colour of liquids.

Loss on drying. Dry to constant weight at 80 °C under reduced pressure (not exceeding 0.6 kPa or about 5 mm of mercury); it loses not more than 20 mg/g.

pH value. pH of a 10 mg/ml solution in carbon-dioxide-free water R, 3.0-5.0.

Related alkaloids. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R1 as the coating substance and a mixture of 9 volumes of chloroform R and 1 volume of methanol R as the mobile phase. Place a sufficient volume of mobile phase to develop the chromatograms and a beaker containing 25 ml of ammonia (~260 g/l) TS into the chromatographic chamber, and equilibrate for 30 minutes. Apply separately to the plate 5 μl of each of 3 solutions in methanol R containing (A) 4.0 mg of the test substance per ml, and (B) 0.12 mg of the test substance per ml, and (C) 0.12 mg of ergometrine hydrogen maleate RS per ml. After removing the plate from the chromatographic chamber, allow it to dry in air until the solvents have evaporated, spray it with 4-dimethylaminobenzaldehyde TS2, and examine the chromatogram in daylight. Any spot obtained with solution A, other than the principal spot, is not more intense than that obtained with solution B.

Assay. Dissolve about 0.20 g, accurately weighed, in 20 ml of glacial acetic acid R1 and 10 ml of acetic anhydride R, and titrate with perchloric acid (0.05 mol/l) VS, as described under 2.6 Non-aqueous titration, Method A. Each ml of perchloric acid (0.05 mol/l) VS is equivalent to 22.07 mg of C19H23N3O2,C4H4O4.

Additional requirements for Ergometrine hydrogen maleate for parenteral use

Complies with the monograph for "Parenteral preparations".

Bacterial endotoxins. Carry out the test as described under 3.4 Test for bacterial endotoxins; contains not more than 700.0 IU of endotoxin RS per mg.

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