Bisoprolol Fumarate Tablets
711
DEFINITION
Bisoprolol Fumarate Tablets contain NLT 90.0% and NMT 105.0% of the labeled amount of bisoprolol fumarate [(C18H31NO4)2·C4H4O4].
IDENTIFICATION
• Thin-Layer Chromatographic Identification Test 201
201
Sample solution:
Equivalent to 40 mg of bisoprolol fumarate, from powdered Tablets (NLT 5), in a 50-mL flask. Add about 20 mL of a mixture of dichloromethane and methanol (7:3), shake for 30 min, centrifuge, and use the clear solution.
Application volume:
20 µL
Developing solvent system:
Dichloromethane, methanol, and ammonia TS, stronger (70: 10: 0.8)
Analysis
Sample:
Sample solution
Proceed as directed in the chapter, except to develop the chromatogram until the solvent front has moved about two-thirds of the length of the plate and to dry the plate in a current of cold air.
ASSAY
• Procedure
Diluent:
Acetonitrile and water (7:13)
Mobile phase:
A 1-L portion of Diluent. Add 5 mL of heptafluorobutyric acid, 5 mL of diethylamine, and 2.5 mL of formic acid.
System suitability solution:
0.5 mg/mL of propranolol hydrochloride and 1 mg/mL of bisoprolol fumarate in Diluent
Standard solution:
1 mg/mL of USP Bisoprolol Fumarate RS in Diluent
Sample solution:
Transfer an equivalent of 25 mg of bisoprolol fumarate, from powdered Tablets (NLT 20), to a 25-mL volumetric flask. Add 10 mL of Diluent, and sonicate for 10 min. Cool, dilute with Diluent to volume, and mix. Centrifuge for 20 min, and use the clear supernatant.
Chromatographic system
Mode:
LC
Detector:
UV 273 nm
Column:
4.6-mm × 12.5-cm; packing L7
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 7.0 between bisoprolol and propranolol, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of (C18H31NO4)2·C4H4O4 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Bisoprolol Fumarate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of bisoprolol fumarate in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–105.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1
Medium:
Water; 900 mL
Apparatus 2:
75 rpm
Time:
20 min
Determine the amount of (C18H31NO4)2·C4H4O4 dissolved by using the following method.
Diluent:
Methanol, triethylamine, phosphoric acid, and water (160: 5: 2.5: 35)
Mobile phase:
Methanol, triethylamine, and water (34:1:50). Adjust with phosphoric acid to a pH of 4.0 ± 0.1.
Standard stock solution:
USP Bisoprolol Fumarate RS in water to obtain a solution having a known concentration of about twice the concentration of bisoprolol fumarate in the Sample solution
Standard solution:
Standard stock solution and Diluent (1:1)
Sample solution:
Sample per Dissolution 711. Withdraw a portion of the solution under test, filter, and dilute with an equal volume of Diluent.
711. Withdraw a portion of the solution under test, filter, and dilute with an equal volume of Diluent.
Chromatographic system
Mode:
LC
Detector:
UV 227 nm
Column:
4.6-mm × 33-
mm;USP35 packing L7
mm;USP35 packing L7
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Tolerances:
NLT 80% (Q) of the labeled amount of (C18H31NO4)2·C4H4O4 is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.5 M sodium chloride; 900 mL
Apparatus 2:
75 rpm
Time:
20 min
Analysis:
Proceed as directed for Test 1 with the following modifications.
Diluent:
Prepare a mixture of methanol, 0.1 N hydrochloric acid, triethylamine, and phosphoric acid (160: 35: 5: 2.5). The dimensions of the column are 4.6 mm × 25 cm.
Tolerances:
NLT 80% (Q) of the labeled amount of (C18H31NO4)2·C4H4O4 is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Bisoprolol Fumarate RS 
2-Propanol, 1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino]-, (±)-, (E)-2-butenedioate (2:1) (salt).
(C18H31NO4)2·C4H4O4 766.96
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2-Propanol, 1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino]-, (±)-, (E)-2-butenedioate (2:1) (salt).
(C18H31NO4)2·C4H4O4 766.96
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2374
Pharmacopeial Forum: Volume No. 36(6) Page 1500