Methysergide 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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1 DEFINITION

Methysergide Maleate contains NLT 97.0% and NMT 103.0% of methysergide maleate (C₂₁H₂₇N₃O₂ · C₄H₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. Thin-Layer Chromatography

Conduct this test without exposure to daylight and with minimum exposure to artificial light.

Standard solution: 5 mg/mL of USP Methysergide Maleate RS in methanol

Sample solution: 5 mg/mL of Methysergide Maleate in methanol

Chromatographic system

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

Adsorbent: 0.25-mm layer of chromatographic silica gel

Application volume: 25 µL

Developing solvent: Chloroform and methanol (20:1)

Spray reagent: 8 mg/mL of p-dimethylaminobenzaldehyde in a cooled mixture of alcohol and sulfuric acid (8:2)

Analysis

Samples: Standard solution and Sample solution

In the chromatographic chamber, place a volume of the Developing solvent sufficient to develop the chromatogram. Place a beaker

containing 25 mL of ammonium hydroxide in the chamber, cover, and allow to equilibrate for 30 min. Apply the Samples, and develop

the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the

developing chamber, mark the solvent front, and allow the solvent to evaporate. Locate the spots on the plate by lightly spraying with

Spray reagent. Allow the plate to dry, then expose it briefly to fumes of a mixture of nitric and hydrochloric acids.

Acceptance criteria: The Rf value of the principal spot of the Sample solution corresponds to that of the Standard solution.

3 ASSAY

Procedure

Sample solution: 200 mg of Methysergide Maleate in 30 mL of glacial acetic acid. Add 1 drop of crystal violet TS.

Analysis: Titrate with 0.1 N perchloric acid VS to a blue endpoint. Perform a blank determination, and make any necessary correction. Each

mL of 0.1 N perchloric acid is equivalent to 46.95 mg of methysergide maleate (C₂₁H₂₇N₃O₂ · C₄H₄O₄).

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

4 IMPURITIES

Ordinary Impurities 〈466〉

Standard solution and Sample solution: Methanol

Eluant: Use the Developing solvent from Identification test B.

Visualization: 1

Acceptance criteria: Meets the requirements

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation 〈781S〉

Sample solution: 2.5 mg/mL in water

Acceptance criteria: +35° to +45°

pH 〈791〉

Sample solution: 1 in 500 in carbon dioxide-free water

Acceptance criteria: 3.7–4.7

Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 120° for 2 h.

Acceptance criteria: NMT 7.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, in a cold place.

USP Reference Standards 〈11〉

USP Methysergide Maleate RS