Methylergometrine Maleate

Edition: BP 2025 (Ph. Eur. 11.6 update)

Methylergometrine Maleate ​

General Notices

(Ph. Eur. monograph 1788)

Action and use

Oxytocic.

Ph Eur

DEFINITION

(6aR,9R)-N-[(1S)-1-(Hydroxymethyl)propyl]-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9- carboxamide (Z)-butenedioate.

Content

99.0 per cent to 101.0 per cent (dried substance).

CHARACTERS

Appearance

White or almost white, hygroscopic, crystalline powder.

Solubility

Soluble in water, slightly soluble in anhydrous ethanol.

IDENTIFICATION

A. Specific optical rotation (see Tests).

B. Infrared absorption spectrophotometry (2.2.24).

Comparison methylergometrine maleate CRS.

TESTS

Solution S

Dissolve 0.100 g in carbon dioxide-free water R and dilute to 20.0 mL with the same solvent.

pH (2.2.3)

4.4 to 5.2.

Dilute 2.0 mL of solution S to 50.0 mL with carbon dioxide-free water R.

Specific optical rotation (2.2.7)

+ 44.0 to + 50.0 (dried substance), determined on solution S.

Related substances

Liquid chromatography (2.2.29). Carry out the test protected from light.

Test solution Dissolve 25 mg of the substance to be examined in 15 mL of mobile phase B and dilute to 50.0 mL with water R.

Reference solution (a) Dilute 1.0 mL of the test solution to 100.0 mL with water R. Dilute 1.0 mL of this solution to 10.0 mL with water R.

Reference solution (b) Dissolve the contents of a vial of methylergometrine for system suitability CRS (containing impurities A, B, C, D, E, F, G, H and I) in 1.0 mL of a mixture of 30 volumes of mobile phase B and 70 volumes of water R.

Column:

— size: l = 0.10 m, Ø = 4.6 mm;

— stationary phase: end-capped octadecylsilyl silica gel for chromatography R (3.5 µm). Mobile phase:

— mobile phase A: 2 g/L solution of ammonium carbamate R;

— mobile phase B: acetonitrile R, water R (50:50 V/V);

Flow rate 2.0 mL/min.

Detection Spectrophotometer at 310 nm.

Injection 20 µL.

Identification of impurities Use the chromatogram supplied with methylergometrine for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B, C, D, E, F, G, H and I.

Relative retention With reference to methylergometrine (retention time = about 12 min): impurity A = about 0.2; impurity B = about 0.5; impurity C = about 0.6; impurity D = about 0.7; impurity I = about 1.10; impurity E = about 1.14; impurity F = about 1.2; impurity G = about 1.3; impurity H = about 1.4.

System suitability Reference solution (b):

— resolution: minimum 3.0 between the peaks due to methylergometrine and impurity I; minimum 1.5 between the peaks due to impurities I and E.

Limits:

— impurity I: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);

— impurity C: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent);

— impurities A, B, D, E, F, G, H: for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent);

— unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);

— total: not more than 6 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.6 per cent);

— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).

Loss on drying (2.2.32)

Maximum 2.0 per cent, determined on 1.000 g by drying in an oven at 105 °C.

Sulfated ash (2.4.14)

Maximum 0.1 per cent, determined on 1.0 g.

ASSAY

Dissolve 0.300 g in 60 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).

1 mL of 0.1 M perchloric acid is equivalent to 45.55 mg of C₂₄H₂₉N₃O₆.

STORAGE

In an airtight container, protected from light.

IMPURITIES

Specified impurities A, B, C, D, E, F, G, H, I.