Cabergoline

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

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

DOWNLOAD PDF HERE

C₂₆H₃₇N₅O₂            451.60

Ergoline-8β-carboxamide, N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)-;

1-[(6-Allylergolin-8β-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea CAS RN: 81409-90-7; UNII: LL60K9J05T.

1 DEFINITION

Cabergoline contains NLT 98.0% and NMT 102.0% of cabergoline (C₂₆H₃₇N₅O₂), calculated on the anhydrous basis for the crystalline form and on the anhydrous and solvent-free basis for the amorphous form.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

Change to read:

B.

Proceed as directed for Procedure 1 or Procedure 2. The criteria for Procedure 1 or Procedure 2 must be met.

Procedure 1: Crystallinity (695)

Acceptance criteria

For the crystalline form: Meets the requirements

For the amorphous form: Does not meet the requirements

Procedure 2: X-Ray Powder Diffraction (941) _{(CN 1-May-2022)}

Acceptance criteria

For the crystalline form: A diffraction pattern is present.

For the amorphous form: No diffraction pattern is present.

3 ASSAY

C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

PROCEDURE

Prepare solutions immediately before use, and protect from light.

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 900 ml. of water, adjust with phosphoric acid to a pH of 2.0, and dilute to 1 L. Add 0.2 mL of triethylamine to the resulting solution and mix.

Mobile phase: Acetonitrile and Buffer (4:21)

Standard solution: 0.25 mg/mL of USP Cabergoline RS in Mobile phase. Sonicate if needed.

Sample solution: 0.25 mg/ml of Cabergoline in Mobile phase. Sonicate if needed.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 25-cm; 10-µm packing L1

Flow rate: 1.3 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1000 theoretical plates

Relative standard deviation: NMT 2.0% for five replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cabergoline (C₂₆H₃₇N₅O₂) in the portion of Cabergoline 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 Cabergoline RS in the Standard solution (mg/mL)

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

Acceptance criteria

For the crystalline form: 98.0%–102.0% on the anhydrous basis

For the amorphous form: 98.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Prepare solutions immediately before use, and protect from light.

Buffer and Mobile phase: Proceed as directed in the Assay.

System suitability solution: To 10 mL of 0.1 M sodium hydroxide add 50 mg of Cabergoline and stir for about 15 min. To 1 ml. of the suspension add 1 mL of 0.1 M hydrochloric acid, and dilute with Mobile phase to 10.0 mL. Sonicate until dissolution is complete. [NOTE-The main degradation product obtained is cabergoline related compound A.]

Sample solution: 0.25 mg/mL of Cabergoline in Mobile phase. Sonicate if needed.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm x 25-cm; 10-µm packing L1

Flow rate: 1.3 mL/min

Injection volume: 100 µL

System suitability

Sample: System suitability solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between cabergoline and cabergoline related compound A

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Cabergoline taken:

Result = (r_u /r_T ) × 100

r_u = peak response of each impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1.

Table 1

^a (6aR,9R,10aR)-N-[3-(Dimethylamino)propyl]-7-(prop-2-enyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide.

^b (6aR,9R,10aR)-N9-[3-(Dimethylamino)propyl]-N4-ethyl-7-(prop-2-enyl)6a,7,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-4,9(6H)-dicarboxamide.

^c (6aR,9R,10aR)-7-(Prop-2-enyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylic acid.

^d (6aR,9R,10aR)-N9-[3-(Dimethylamino)propyl]-N4-ethyl-N9-(ethylcarbamoyl)-7-(prop-2-enyl)-6a,7,8,9,10,10a-hexahydroindolo[4,3- fg]quinoline-4,9(6H)-dicarboxamide.

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation (781S)

Sample solution: 1 mg/mL in alcohol

Acceptance criteria

For the crystalline form: -77" to -83" on the anhydrous basis

For the amorphous form: -77" to -83" on the anhydrous and solvent-free basis

WATER DETERMINATION, Method / (921)

Acceptance criteria

For the crystalline form: NMT 0.5%

For the amorphous form: NMT 1.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, protected from light. If it is labeled as amorphous, preserve under nitrogen in tight containers, store cold, and protect from light.

LABELING: Where it is the amorphous form, the label so indicates.

USP REFERENCE STANDARDS (11)

USP Cabergoline RS