Balsalazide Disodium Capsules

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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2 DEFINITION

Balsalazide Disodium Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of balsalazide disodium (C₁₇H₁₃N₃Na₂O₆·2H₂O).

3 IDENTIFICATION

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

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Using a 0.2-cm cell, record the UV spectrum of the Sample solution, obtained in the Assay, in the range of 200–400 nm: it exhibits maxima at about 261 nm and 357 nm.

4 ASSAY

Procedure

Buffer: Add 5 mL of triethylamine to 1000 mL of water, and adjust with phosphoric acid to a pH of 6.00 ± 0.1.

Mobile phase: Acetonitrile and Buffer (1:4)

Diluent: Water

Standard solution: 60 µg/mL of USP Balsalazide Disodium RS in Diluent. [Note—Use sonication as necessary.]

Sample stock solution: Transfer an equivalent to 150 mg of balsalazide disodium, from the Capsules contents, to a 100-mL volumetric flask, add 70 mL of Diluent, sonicate for 5 min, and dilute with Diluent to volume.

Sample solution: 60 µg/mL of balsalazide disodium, from the Sample stock solution, in Diluent. Pass a portion of this solution through a suitable filter, discarding the first 3 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 360 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 10,000 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Sample: Standard solution and Sample solution

Calculate the percentage of the labeled amount of C₁₇H₁₃N₃Na₂O₆·2H₂O in the portion of Capsules 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 Balsalazide Disodium RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of balsalazide disodium in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

5 IMPURITIES

Organic Impurities

Procedure

Buffer: Dissolve 2.7 g of monobasic potassium phosphate in 1000 mL of water, and adjust with 10% potassium hydroxide solution to a pH of 6.00 ± 0.1.

Diluent: Water

Solution A: Buffer

Solution B: Acetonitrile

Sample solution: Transfer an amount of finely crushed powder equivalent to 100 mg of balsalazide disodium to a 100-mL volumetric flask, add 70 mL of Diluent, sonicate for 5 min, and dilute with Diluent to volume. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size.

Standard solution: 1.0 µg/mL of USP Balsalazide Disodium RS in Diluent

System suitability solution: 1.0 µg/mL of USP Balsalazide Disodium RS, 1.5 µg/mL of USP Balsalazide Related Compound A RS, 0.5 µg/mL of USP Balsalazide Related Compound B RS, and 0.5 µg/mL of USP Salicylic Acid RS in Diluent

Mobile phase: See the gradient table below.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection size: 30 µL

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 5 between balsalazide and balsalazide related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Tailing factor: NMT 1.5, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (rᵢ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵢ = peak response for each individual impurity from the Sample solution

rₛ = peak response for the balsalazide peak from the Standard solution

Cₛ = concentration of USP Balsalazide Disodium RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of balsalazide disodium in the Sample solution, based on the label claim (mg/mL)

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Reporting level for impurities: 0.05%

Total impurities: NMT 1.0%. [Note—When reporting results for Individual impurities and Total impurities, disregard peaks corresponding to salicylic acid and balsalazide related compound B, as these impurities are controlled in the drug substance only.]

a. (E)-5-[(p-Carboxyphenyl)azo]-2-salicylic acid.

b. (E)-5-({m-[(2-Carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid.

6 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: pH 6.8 phosphate buffer; 900 mL

Apparatus 2: 50 rpm, with stainless steel wire helix sinkers

Time: 30 min

Detector: UV 357 nm, with background correction at 590 nm

Path length: 0.02-cm flow cell

Blank: Medium

Standard solution: 0.83 mg/mL of USP Balsalazide Disodium RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 20-µm pore size.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₇H₁₃N₃Na₂O₆·2H₂O dissolved:

Result = (Aᵤ/Aₛ) × C × V × (100/L)

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

C = concentration of USP Balsalazide Disodium RS in the Standard solution (mg/mL)

V = volume of Medium (mL), 900

L = Capsule label claim (mg)

Tolerances: NLT 70% (Q) of the labeled amount of C₁₇H₁₃N₃Na₂O₆·2H₂O is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Balsalazide Disodium RS

USP Balsalazide Related Compound A RS

(E)-5-[(p-Carboxyphenyl)azo]-2-salicylic acid, disodium salt. C₁₄H₈N₂O₅Na₂ 330.21

USP Balsalazide Related Compound B RS

(E)-5-({m-[(2-Carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid. C₁₇H₁₅N₃O₆ 357.32

USP Salicylic Acid RS