Balsalazide Disodium

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

1 DEFINITION

Balsalazide Disodium contains NLT 98.0% and NMT 102.0% of C₁₇H₁₃N₃Na₂O₆·2H₂O, calculated on the as-is basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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

Sample solution: 10 µg/mL in water

C. Identification Tests—General, Sodium 〈191〉

3 ASSAY

Procedure

Sample: 219 mg

Analysis: Add 80 mL of glacial acetic acid to the Sample, sonicate to dissolve, and 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 21.87 mg of C₁₇H₁₃N₃Na₂O₆·2H₂O.

Acceptance criteria: 98.0%–102.0% on the as-is basis

4 IMPURITIES

Organic Impurities

[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. Procedure 2 is recommended when impurities 1, 2, and 3 listed in Impurity Table 2 may be present.]

Procedure 1

Solution A: 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: Use Solution A.

Solution B: Use acetonitrile.

Standard solution: 0.5 µg/mL of USP Balsalazide Disodium RS, 0.5 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. If needed, a small amount of acetonitrile may be added to facilitate dissolution.

Sample solution: 1 mg/mL of Balsalazide Disodium in Diluent

Mobile phase: See the gradient table below.

Chromatographic system

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

Sample: Standard solution

Suitability requirements

Resolution: NLT 5 between balsalazide and balsalazide related compound B

Relative standard deviation: NMT 5% for each peak

Tailing factor: NMT 1.8 for the balsalazide peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Balsalazide Disodium taken:

Result = (r₍ᵤ₎/r₍ₛ₎) × (C₍ₛ₎/C₍ᵤ₎) × 100

r₍ᵤ₎ = peak response for each individual impurity from the Sample solution

r₍ₛ₎ = peak response for the corresponding impurity from the Standard solution. For unspecified impurities, r₍ₛ₎ is the peak response for the balsalazide peak from the Standard solution.

C₍ₛ₎ = concentration of the corresponding impurity in the Standard solution (mg/mL). For unspecified impurities, C₍ₛ₎ is the concentration of balsalazide disodium in the Standard solution.

C₍ᵤ₎ = concentration of Balsalazide Disodium in the Sample solution (mg/mL)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Reporting level for impurities: 0.03%

Total impurities: NMT 1.0%

¹ (E)-5-[(p-Carboxyphenyl)azo]-2-salicylic acid.

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

Procedure 2

Solution A: Prepare 50 mM monobasic potassium phosphate buffer as follows: Dissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water, and adjust with 2 N potassium hydroxide solution to a pH of 6.8–7.0.

Solution B: Acetonitrile, methanol and Solution A (5:1:14)

Solution C: Acetonitrile, methanol and Solution A (9:1:10)

Diluent: Use Solution B.

Mobile phase: See the gradient table below.

Standard solution: 0.075 mg/mL of USP Balsalazide Disodium RS in Diluent.

Sensitivity solution: 0.375 µg/mL in Diluent, from Standard solution

System suitability solution: 1.5 mg/mL of USP Balsalazide Disodium RS and 1.5 µg/mL of USP Balsalazide Related Compound A RS in Diluent

Sample solution: 1.5 mg/mL of Balsalazide Disodium in Diluent.

Chromatographic system

Mode: LC

Detector: UV 300 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 25°–27°

Flow rate: 1 mL/min

Injection size: 10 µL

System suitability

Samples: Standard solution, Sensitivity solution, and System suitability solution

Suitability requirements

Resolution: NLT 8.5 between balsalazide related compound A and balsalazide, from the System suitability solution

Tailing factor: NMT 3.4 for the balsalazide peak, from the System suitability solution

Signal-to-noise ratio: NLT 10, from the Sensitivity solution

Relative standard deviation: NMT 2.0%, from the Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Balsalazide Disodium taken:

Result = (r₍ᵤ₎/r₍ₛ₎) × (C₍ₛ₎/C₍ᵤ₎) × (1/F) × 100

r₍ᵤ₎ = peak response for each individual impurity from the Sample solution

r₍ₛ₎ = peak response for balsalazide from the Standard solution

C₍ₛ₎ = concentration of USP Balsalazide Disodium RS in the Standard solution

C₍ᵤ₎ = concentration of Balsalazide Disodium in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 2)

Acceptance criteria

Individual impurities: See Impurity Table 2.

Reporting level for impurities: 0.03%

Total impurities: NMT 0.50%

¹ This impurity may be present as two peaks. Use the sum of the two peaks to determine compliance.

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

³ (E,E)-3,5-di-[4-(2-Carboxyethylcarbamoyl) phenylazo]-salicylic acid.

⁴ (E)-3-[4-(2-Carboxyethylcarbamoyl) phenylazo]-salicylic acid.

⁵ (E,E)-5-{{2-[4-(2-Carboxyethylcarbamoyl)phenylazo]-4-[2-carboxyethyl-carbamoyl]}phenylazo}-salicylic acid.

⁶ (E)-2-[4-(2-Carboxyethylcarbamoyl)phenoxy]-5-{[4-(2-carboxyethyl-carbamoyl)]phenylazo}-benzoic acid

⁷ (E)-2-Hydroxy-5-[[4-[[(3-isopropoxy-3-oxopropyl)amino]carbonyl]phenyl]azo]benzoic acid

5 SPECIFIC TESTS

Water Determination, Method Ia 〈921〉: 7.8%–9.0%

6 ADDITIONAL REQUIREMENTS

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

Labeling: If a test for Organic Impurities other than Test 1 is used, the labeling states the test with which the article complies.

Change to read:

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▲ (CN 1-Dec-2024)

USP Balsalazide Related Compound B RS

(E)-5-({m-[(2-Carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid. C₁₇H₁₅N₃O₆ ▲357.32▲ (CN 1-Dec-2024)

USP Salicylic Acid RS