Salicylic Acid

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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C₇H₆O₃ 138.12

Benzoic acid, 2-hydroxy-;

Salicylic acid

CAS RN^®: 69-72-7; UNII: O414PZ4LPZ.

1 DEFINITION

Salicylic Acid contains NLT 98.0% and NMT 102.0% of salicylic acid (C₇H₆O₃), 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.

3 ASSAY

3.1 Procedure

Mobile phase: Methanol, glacial acetic acid, and water (40:1:60), prepared by adding 10 mL of glacial acetic acid to a solution containing 400 mL of methanol and 600 mL of water.

Standard solution: 0.5 mg/mL of USP Salicylic Acid RS in Mobile phase. Sonicate to dissolve as needed.

Sample solution: 0.5 mg/mL of Salicylic Acid in Mobile phase. Sonicate to dissolve as needed.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 10-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of salicylic acid (C₇H₆O₃) in the portion of Salicylic Acid 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 Salicylic Acid RS in the Standard solution (mg/mL)

C_U = concentration of Salicylic Acid in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.05%

4.2 Chloride and Sulfate, Chloride 〈221〉

Sample: 1.5 g

Analysis: Heat the Sample with 75 mL of water until it is dissolved. Cool, add water to restore the original volume, and filter.

Acceptance criteria: A 25-mL portion of the filtrate shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid. (0.014%)

4.3 Chloride and Sulfate, Sulfate 〈221〉

Sample solution: 1.0 g in alcohol and water (1:1)

Acceptance criteria: No more sulfate than corresponds to 0.2 mL of 0.020 N sulfuric acid (0.02%)

4.4 Organic Impurities

Mobile phase: Prepare as directed in the Assay.

Diluent: Methanol, glacial acetic acid, and water (70:4:30)

Standard solution: 0.5 mg/mL of USP Salicylic Acid RS, 0.05 mg/mL of USP Salicylic Acid Related Compound A RS, 0.025 mg/mL of USP Salicylic Acid Related Compound B RS, and 0.01 mg/mL of USP Phenol RS in Diluent.

Peak identification solution: 0.01 mg/mL of USP Phenol RS in Diluent.

Sample solution: 50 mg/mL of Salicylic Acid in Diluent. Sonicate until completely dissolved.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 10-cm; 5-µm packing L1

Flow rate: 0.5 mL/min

Injection volume: 2 µL

System suitability

Samples: Standard solution and Peak identification solution

Suitability requirements

[Note—Identify the elution order of phenol by comparing with the Peak identification solution.]

Resolution: NLT 2.0 between any two peaks, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of salicylic acid related compound A, salicylic acid related compound B, and phenol in the portion of Salicylic Acid taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of salicylic acid related compound A, salicylic acid related compound B, or phenol from the Sample solution

r_S = peak response of salicylic acid related compound A, salicylic acid related compound B, or phenol from the Standard solution

C_S = concentration of USP Salicylic Acid Related Compound A RS, USP Salicylic Acid Related Compound B RS, or USP Phenol RS in the Standard solution (mg/mL)

C_U = concentration of Salicylic Acid in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Salicylic Acid taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any other individual impurity from the Sample solution

r_S = peak response of salicylic acid related compound B from the Standard solution

C_S = concentration of USP Salicylic Acid Related Compound B RS in the Standard solution (mg/mL)

C_U = concentration of Salicylic Acid in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. [Note—The elution order for salicylic acid related compound B and phenol may switch.]

Table 1

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry over silica gel for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Phenol RS

USP Salicylic Acid RS

USP Salicylic Acid Related Compound A RS

4-Hydroxybenzoic acid

C₇H₆O₃ 138.12

USP Salicylic Acid Related Compound B RS

4-Hydroxyisophthalic acid

C₈H₆O₅ 182.13