Aminobenzoate Sodium

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

C₇H₆NNaO₂ 159.12

Benzoic acid, 4-amino-, sodium salt;

Sodium 4-aminobenzoate CAS RN^®: 555-06-6; UNII: 75UI7QUZ5J.

1 DEFINITION

Aminobenzoate Sodium contains NLT 98.0% and NMT 102.0% of aminobenzoate sodium (C₇H₆NNaO₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K _{(CN 1-May-2020)}

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. • C. Identification Tests—General 〈191〉, Chemical Identification Tests, Sodium: A solution (1 in 100) meets the requirements of the ame test.

3 ASSAY

3.1 Procedure

Solution A: 1.5% acetic acid, prepared by mixing 690 mL of water with 10 mL of glacial acetic acid, and passing through a suitable lter of 0.45-µm pore size

Mobile phase: Methanol and Solution A (15:85)

Standard solution: 0.1 mg/mL of USP Aminobenzoate Sodium RS in Mobile phase. Sonicate to dissolve.

Sample solution: 0.1 mg/mL of Aminobenzoate Sodium in Mobile phase. Sonicate to dissolve.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.0-mm × 15-cm; 3.5-µm packing L11

Flow rate: 0.35 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of aminobenzoate sodium (C₇H₆NNaO₂) in the portion of Aminobenzoate Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Aminobenzoate Sodium RS in the Standard solution (mg/mL)

C_U = concentration of Aminobenzoate Sodium in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

4.1 Limit of Aniline and p-Toluidine

Diluent: Methylene chloride

Standard stock solution: 0.1 mg/mL each of USP Aniline RS and USP p-Toluidine RS in Diluent

Standard solution: 1.0 µg/mL each of USP Aniline RS and USP p-Toluidine RS in Diluent from Standard stock solution Sample solution: 100 mg/mL of Aminobenzoate Sodium in Diluent prepared as follows. Add an appropriate quantity of Aminobenzoate Sodium to a suitable volumetric ask and dilute with Diluent to volume. Agitate for 10 min on a shaker and centrifuge at 3000 rpm for 5 min. Use the supernatant.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detectors

Flame ionization: 300°

Hydrogen: 40 mL/min

Air: 400 mL/min

Column: 30-m × 0.32-mm fused silica capillary; coated with 0.5-µm lm of phase G27

Temperatures

Injection port: 280°

Detector: 300°

Column: See Table 1.

Table 1

Carrier gas: Helium Flow rate: 1 mL/min

Injection volume: 2 µL

Injection type: Split ratio, 1:10

System suitability

Sample: Standard solution

[Note—The relative retention times of aniline and p-toluidine are about 4.1 and 5.1 min, respectively.] Suitability requirements

Resolution: NLT 7.0 between aniline and p-toluidine

Tailing factor: NMT 1.5 for aniline and p-toluidine

Relative standard deviation: NMT 6.0% for aniline and p-toluidine

4.1.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of p-toluidine or aniline in the portion of Aminobenzoate Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of p-toluidine or aniline from the Sample solution

r_S = peak response of p-toluidine or aniline from the Standard solution

C_S = concentration of the corresponding USP Reference Standard in the Standard solution (mg/mL)

C_U = concentration of Aminobenzoate Sodium in the Sample solution (mg/mL)

4.1.3 Acceptance criteria

Aniline: NMT 10 ppm

p-Toluidine: NMT 20 ppm

4.2 Organic Impurities

Solution A: 1.5% acetic acid, prepared by mixing 690 mL of water with 10 mL of glacial acetic acid

Solution B: Methanol

Mobile phase: See Table 2. 

Table 2

Diluent: Methanol and water (85:15)

System suitability solution: 1 mg/mL of USP Aminobenzoate Sodium RS, 0.01 mg/mL of USP 4-Nitrobenzoic Acid RS, and 0.01 mg/mL of USP Benzocaine RS in Diluent prepared as follows. Transfer 1 mL each of 0.1 mg/mL of USP 4-Nitrobenzoic Acid RS in methanol and 0.1 mg/mL of USP Benzocaine RS in Diluent to a 10-mL volumetric ask containing the appropriate amount of USP Aminobenzoate Sodium RS, and dilute with Diluent to volume.

Standard solution: 1 µg/mL each of USP Aminobenzoate Sodium RS, USP 4-Nitrobenzoic Acid RS, and USP Benzocaine RS in Diluent.

Sample solution: 1 mg/mL of Aminobenzoate Sodium in Diluent

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.0-mm × 15-cm; 3.5-µm packing L11

Flow rate: 0.4 mL/min

Injection volume: 5 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between benzocaine and 4-nitrobenzoic acid, System suitability solution

Relative standard deviation: NMT 3% for the aminobenzoate sodium, 4-nitrobenzoic acid, and benzocaine peaks, Standard solution

4.2.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 4-nitrobenzoic acid or benzocaine in the portion of Aminobenzoate Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of 4-nitrobenzoic acid or benzocaine from the Sample solution

r_S = peak response of 4-nitrobenzoic acid or benzocaine from the Standard solution

C_S = concentration of USP 4-Nitrobenzoic Acid RS or USP Benzocaine RS in the Standard solution (mg/mL)

C_U = concentration of Aminobenzoate Sodium in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecified impurity in the portion of Aminobenzoate Sodium taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of any unspecied impurity from the Sample solution

r_S = peak response of aminobenzoate from the Standard solution

C_S = concentration of USP Aminobenzoate Sodium RS in the Standard solution (mg/mL)

C_U  = concentration of Aminobenzoate Sodium in the Sample solution (mg/mL)

Acceptance criteria: See Table 3. 

Table 3

5 SPECIFIC TESTS

5.1 pH 〈791〉

Sample solution: 50 mg/mL

Acceptance criteria: 8.0–9.0

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Aminobenzoate Sodium RS

USP Aniline RS

Aniline.

C₆H₇N        93.13

USP Benzocaine RS

USP 4-Nitrobenzoic Acid RS

4-Nitrobenzoic acid.

C₇H₅NO₄     167.12

USP p-Toluidine RS

4-Methylaniline.

C₇H₉N       107.16