Bisoprolol Fumarate Tablets

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

Bisoprolol Fumarate Tablets contain NLT 90.0% and NMT 105.0% of the labeled amount of bisoprolol fumarate [(C₁₈H₃₁NO₄)₂ . C₄H₄O₄].

2 IDENTIFICATION

2.1 THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (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.

3 ASSAY

3.1 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

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 273 nm

Column: 4.6-mm x 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 = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Bisoprolol Fumarate RS in the Standard solution (mg/mL)

C_U = nominal concentration of bisoprolol fumarate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-105.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Test 1

Medium: Water; 900 mL

Apparatus 2: 75 rpm

Time: 20 min

Determine the amount of (C18H3, NO2), C₂H₂O, 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.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 227 nm

Column: 4.6 - mm * 33 - mm 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 x 25 cm.

Tolerances: NLT 80% (Q) of the labeled amount of (C₁₈H₃₁NO₄)₂ . C₄H₄O₄ is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 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)

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