Bromocriptine Mesylate
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)
[22260-51-1].
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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)
[22260-51-1].DEFINITION
Bromocriptine Mesylate contains NLT 98.0% and NMT 102.0% of C32H40BrN5O5·CH4SO3, calculated on the dried basis.
IDENTIFICATION
• A. Infrared Absorption 
197M
:
Undried
197M:
Undried
• B. Ultraviolet Absorption 197U
197U
Sample solution:
50 µg/mL in 0.1 M methanolic methanesulfonic acid
Acceptance criteria:
Meets the requirements
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·CH4SO3.
541). Each mL of 0.1 N perchloric acid is equivalent to 75.07 mg of C32H40BrN5O5·CH4SO3.
Acceptance criteria:
98.0%–102.0% on the dried basis
IMPURITIES
Organic Impurities
• 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.
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
• 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.
| Time (min) |
Solution B (%) |
Solution C (%) |
|---|---|---|
| 0 | 100 | 0 |
| 18 | 100 | 0 |
| 30 | 0 | 100 |
| 40 | 0 | 100 |
| 41 | 100 | 0 |
System suitability solution:
2.0 mg/mL each of -ergocryptine and Bromocriptine Mesylate in Diluent
-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
Mode:
LC
Detector:
UV 300 nm
Column:
4.6-mm × 15-cm; 3-µm 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 -ergocryptine and bromocriptine mesylate are 0.46 and 1.0, respectively. ]
-ergocryptine and bromocriptine mesylate are 0.46 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 15 between -ergocryptine and bromocriptine mesylate, System suitability solution
-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 = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of bromocriptine from the Standard solution |
| CS | = | = concentration of USP Bromocriptine Mesylate RS in the Standard solution (mg/mL) |
| CU | = | = 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%
SPECIFIC TESTS
• Color of Solution 631
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
781S
Sample solution:
10 mg/mL, in a mixture of methylene chloride and methanol (1:1)
Acceptance criteria:
+95
to +105
to +105
• Loss on Drying
(See Thermal Analysis 891.)
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 flow rate of 45 mL/min. Record the thermogram from ambient temperature to 160.
/min in an atmosphere of nitrogen at a flow rate of 45 mL/min. Record the thermogram from ambient temperature to 160.
Acceptance criteria:
It loses NMT 4.0% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, in a cold place.
• USP Reference Standards 11
11
USP Bromocriptine Mesylate RS 
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Domenick Vicchio, Ph.D.
Senior Scientific Liaison 1-301-998-6828 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2387
Pharmacopeial Forum: Volume No. 36(5) Page 1173