Bromocriptine Mesylate

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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C₃₂H₄₀BrN₅O₅ · CH₄SO₃            750.70

Ergotaman-3',6',18-trione, 2-bromo-12-hydroxy-2'-(1-methylethyl)-5-(2-methylpropyl)-, monomethanesulfonate (salt), (5')-;

2-Bromoergocryptine monomethanesulfonate (salt) CAS RN: 22260-51-1; UNII: FFP983J3OD.

1 DEFINITION

Bromocriptine Mesylate contains NLT 98.0% and NMT 102.0% of C₃₂H₄₀BrN₅O₅ · CH₄SO₃ calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{(CN 1-Mar-2020)}: Undried

Change to read:

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 _{(CN 1-May-2020)}

Sample solution: 50 µg/mL in 0.1 M methanolic methanesulfonic acid

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Sample solution: 600 mg of Bromocriptine Mesylate

Analysis: Dissolve with 80 mL of a mixture of acetic anhydride and glacial acetic acid (7:1). Titrate with 0.1 N perchloric acid VS. Perform a blank determination, and make any necessary correction (see Titrimetry (541)). Each mL of 0.1 N perchloric acid is equivalent to 75.07 mg of C₃₂H₄₀BrN₅O₅

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

4.1 PROCEDURE 1: LIMIT OF METHANESULFONIC ACID CONTENT

Sample solution: 400 mg of Bromocriptine Mesylate

Analysis: Dissolve with 70 mL of methanol. Titrate under nitrogen with 0.1 N methanolic potassium hydroxide VS. Perform a blank determination, and make any necessary correction (see Titrimetry (541)). Each mL of 0.1 N methanolic potassium hydroxide is equivalent to 9.61 mg of CH₃SO₃H.

Acceptance criteria: NLT 12.5% and NMT 13.4% of CH₃SO₃H on the dried basis

4.2 PROCEDURE 2

Solution A: 0.1 N citric acid solution. Adjust with hydrochloric acid to a pH of 2.0.

Diluent: Methanol and Solution A (1:1)

Solution B: Acetonitrile and 0.01 M phosphate buffer, pH 7.0 (2:3)

Solution C: Acetonitrile and 0.01 M phosphate buffer, pH 7.0 (3:2)

Mobile phase: See the gradient table below.

System suitability solution: 2.0 mg/mL each of a-ergocryptine and Bromocriptine Mesylate in Diluent

Standard stock solution: 46 µg/mL of USP Bromocriptine Mesylate RS in methanol and Solution A (1:1). [NOTE-Dissolve in 50% of the flask volume of methanol and dilute with Solution A to volume.]

Standard solution: 4.6 µg/mL of USP Bromocriptine Mesylate RS in Diluent from the Standard stock solution

Sample solution: 4.6 mg/mL of Bromocriptine Mesylate in methanol and Solution A (1:1). [NOTE-Dissolve in 50% of the flask volume of methanol and dilute with Solution A to volume.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 300 nm

Column: 4.6-mm x 15-cm; 3-um packing L1

Flow rate: 2 mL/min

Injection size: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for a-ergocryptine and bromocriptine mesylate are 0.46 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 15 between a-ergocryptine and bromocriptine mesylate, System suitability solution

Tailing factor: NMT 1.5, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

[NOTE-The relative retention times for bromocriptine and bromocriptinine are 1.0 and 1.7, respectively.]

Calculate the percentage of each impurity in the portion of Bromocriptine Mesylate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of bromocriptine from the Standard solution

C_s = concentration of USP Bromocriptine Mesylate RS in the Standard solution (mg/mL)

C_u = concentration of Bromocriptine Mesylate in the Sample solution (mg/mL)

F = relative response factor equal to 1.4 for any peak eluting at a relative retention time of about 0.9 or less, and equal to 1.0 for all other peaks

Acceptance criteria

Individual impurities: NMT 0.4% of bromocriptinine is found; NMT 0.1% of any individual impurity is found.

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Color of Solution 〈631〉

Matching solutions: Prepare three solutions, A, B, and C, containing, respectively, the following parts of cobaltous chloride CS, ferric chloride

CS, cupric sulfate CS, and dilute hydrochloric acid (1 in 40).

A: 3.0:3.0:2.4:31.6

B: 1.0:2.4:0.4:36.2

C: 0.6:2.4:0:37.0

Sample solution: 10 mg/mL of Bromocriptine Mesylate in methanol

Analysis: Compare the Sample solution with 10-mL portions of the Matching solutions in suitable matched tubes.

Acceptance criteria: The solution is clear and not darker in color than Matching solutions A, B, and C.

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL, in a mixture of methylene chloride and methanol (1:1)

Acceptance criteria: +95° to +105°

Loss on Drying

(See Thermal Analysis 〈891〉.)

Analysis: Determine the percentage of volatile substances by thermogravimetric analysis using 10 mg of Bromocriptine Mesylate. Heat the specimen under test at the rate of 10°/min in an atmosphere of nitrogen at a ow rate of 45 mL/min. Record the thermogram from ambient temperature to 160°.

Acceptance criteria: It loses NMT 4.0% of its weight.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Bromocriptine Mesylate RS