Methylergonovine Maleate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₀H₂₅N₃O₂ . C₄H₄O₄ 455.50

Ergoline-8-carboxamide, 9,10-didehydro-N-[1-(hydroxy methyl)propyl]-6-methyl-, [8β(S)]-, (Z)-2-butenedioate (1:1) (salt);

9,10-Didehydro-N-[(S)-1-(hydroxymethyl)propyl]-6-methylergoline-8β-carboxamide maleate (1:1) (salt) CAS RN^®: 57432-61-8; UNII: IR84JPZ1RK.

1 DEFINITION

Methylergonovine Maleate contains NLT 97.0% and NMT 103.0% of methylergonovine maleate (C₂₀H₂₅N₃O₂ . C₄H₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The R_F values of the principal fluorescent spot and the principal blue spot of the Sample solution correspond to those of the Standard stock solution, as obtained in the test for Related Alkaloids.

3 ASSAY

3.1 PROCEDURE

Conduct this procedure with a minimum exposure to light.

Mobile phase: Acetonitrile and 2.0 g/L of monobasic potassium phosphate (1:4)

Diluent: 2.5 mg/mL of tartaric acid prepared as follows. Transfer a suitable amount of tartaric acid to a suitable volumetric flask, add 50% of the flask volume of water, and mix with shaking. Dilute with methanol to volume. Allow the mixture to cool before use.

Standard stock solution: 0.1 mg/mL of USP Methylergonovine Maleate RS in Diluent. Shake by mechanical means for 15 min.

Standard solution: 4 µg/mL of USP Methylergonovine Maleate RS from the Standard stock solution in Diluent

Sample stock solution: 0.2 mg/mL of Methylergonovine Maleate in Diluent. Shake by mechanical means for 15 min or until completely dissolved.

Sample solution: 4 µg/mL of Methylergonovine Maleate from the Sample stock solution in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Fluorescence with excitation at 315 nm and emission at 423 nm

Column: 4.6-mm × 25-cm; packing L7

Temperature: 30°

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methylergonovine maleate (C₂₀H₂₅N₃O₂ . C₄H₄O₄) in the portion of Methylergonovine Maleate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Methylergonovine Maleate RS in the Standard solution (µg/mL)

C_U = nominal concentration of the Sample solution (µg/mL)

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

RELATED ALKALOIDS

Conduct this test promptly, without exposure to daylight and with minimum exposure to artificial light. Solutions containing methylergonovine maleate should be prepared immediately before use.

Diluent: Alcohol and ammonium hydroxide (9:1)

Standard stock solution: 10 mg/mL of USP Methylergonovine Maleate RS in Diluent

Standard solution A: 0.20 mg/mL of USP Methylergonovine Maleate RS from the Standard stock solution in Diluent

Standard solution B: 0.10 mg/mL of USP Methylergonovine Maleate RS from the Standard stock solution in Diluent

Standard solution C: 0.05 mg/mL of USP Methylergonovine Maleate RS from the Standard stock solution in Diluent

Sample solution: 10 mg/mL of Methylergonovine Maleate in Diluent

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 5 µL

Developing solvent system: Chloroform, methanol, and water (75:25:3), equilibrated for 30 min

Spray reagent: 10 mg/mL of p-dimethylaminobenzaldehyde in a cooled mixture of alcohol and hydrochloric acid (1:1)

Analysis

Samples: Standard stock solution, Standard solution A, Standard solution B, Standard solution C, and Sample solution

Proceed as directed in the chapter. Locate the spots on the plate by spraying thoroughly and evenly with Spray reagent. Immediately dry in a stream of nitrogen for 2 min.

Acceptance criteria: The Rf value of the principal spot of the Sample solution corresponds to that of the Standard stock solution. Estimate the concentration of any other spots observed from the Sample solution by comparison with Standard solution A, Standard solution B, and Standard solution C. The spots from Standard solution A, Standard solution B, and Standard solution C are equivalent to 2.0%, 1.0%, and 0.50% of impurities, respectively. The sum of the impurities is NMT 2.0%.

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION 〈781S〉, Specific Rotation

Sample solution: 5 mg/mL of Methylergonovine Maleate in water

Acceptance criteria: +44° to +50°

5.2 pH 〈791〉

Sample solution: 0.2 mg/mL of Methylergonovine Maleate in water

Acceptance criteria: 4.4–5.2

5.3 LOSS ON DRYING 〈731〉

Analysis: Dry under vacuum at 80° to constant weight.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store in a cold place.

USP Reference Standards 〈11〉

USP Methylergonovine Maleate RS