Allantoin

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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C₄H₆N₄O₃ 158.12 

Urea, (2,5-dioxo-4-imidazolidinyl)-; 

Allantoin CAS RN®: 97-59-6; UNII: 344S277G0Z. 

1 DEFINITION 

Allantoin contains NLT 98.5% and NMT 101.0% of C₄H₆N₄O₃. 

2 IDENTIFICATION 

Change to read:

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

B. Thin-Layer Chromatographic Identification Test 〈201〉: The R_F value of the principal spot from Sample solution B corresponds to that from Standard solution A, as described in the test for Organic Impurities. 

3 ASSAY 

Procedure 

Sample: 120 mg 

Analysis: Transfer the Sample to a 100-mL beaker, dissolve by stirring in 40 mL of water, and titrate with 0.1 M sodium hydroxide. Use a suitable electrode system (see Titrimetry 〈541〉). Each mL of 0.1 M sodium hydroxide is equivalent to 15.81 mg of C₄H₆N₄O₃.

Acceptance criteria: 98.5%–101.0% 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.1% 

Organic Impurities 

Adsorbent: Cellulose 

Diluent: Methanol and water (1:1) 

Urea stock solution: 1 mg/mL of USP Urea RS in water 

Standard solution A: 1 mg/mL of USP Allantoin RS in Diluent 

Standard solution B: 0.1 mg/mL of USP Urea RS in methanol, from Urea stock solution 

Standard solution C: Standard solution A and Standard solution B (1:1) 

Sample solution A: Transfer 0.10 g of Allantoin to a 10-mL volumetric ask, add 5 mL of water, dissolve by heating, and allow to cool. Dilute with methanol to volume. [Note—Use immediately after preparation.] 

Sample solution B: Transfer 1 mL of Sample solution A to a 10-mL volumetric ask, and dilute with Diluent to volume. Spray reagent: 5 mg/mL of p-dimethylaminobenzaldehyde in a mixture of methanol and hydrochloric acid (3:1) 

Application volume 

Standard solution A: 5 µL 

Standard solution B: 5 µL 

Standard solution C: 5 µL 

Sample solution A: 10 µL 

Sample solution B: 5 µL 

Developing solvent system: Butyl alcohol, glacial acetic acid, and water (60:15:25) 

Analysis: Proceed as directed for Chromatography 〈621〉, Thin-Layer Chromatography. Develop the chromatogram until the solvent front has moved about 10 cm. Spray the plate with Spray reagent, dry in a current of hot air, and after 30 min examine under visible light. Acceptance criteria: Any spot from Sample solution A, except for the principal spot, is not more intense than the spot from Standard solution B (NMT 0.5%). The test is not valid unless the principal spots from Standard solution C are clearly separated. 

5 SPECIFIC TESTS

5.1 Acidity or Alkalinity

Sample solution: 5 mg/mL in carbon dioxide-free water

Analysis: To 5 mL of the Sample solution add 5 mL of water, 0.1 mL of methyl red TS, and 0.2 mL of 0.01 M sodium hydroxide. Acceptance criteria: A yellow color is observed. The solution turns red upon the addition of 0.4 mL of 0.01 M hydrochloric acid.

Loss on Drying 〈731〉: Dry a sample at 105° to constant weight: it loses NMT 0.1% of its weight.

5.2 Reducing Substances

Sample solution: 1.0 g of Allantoin in 10 mL of water. Shake for 2 min, and filter.

Analysis: To the Sample solution add 1.5 mL of 0.02 M potassium permanganate.

Acceptance criteria: The solution remains violet for at least 10 min.

6 ADDITIONAL REQUIREMENTS

USP Reference Standards 〈11〉

USP Allantoin RS

USP Urea RS