Urea

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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CH₄N₂O    60.06

Urea;

Carbamide CAS RN: 57-13-6; UNII: 8W8T17847W.

1 DEFINITION

Urea contains NLT 98.0% and NMT 102.0% of urea (CH₄N₂O).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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

PROCEDURE

Solution A: Transfer 1 mL of formic acid to a 1-L volumetric flask and dilute with water to volume.

Solution B: 100% Acetonitrile, passed through a membrane filter of 0.2-um pore size

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (90:10)

System suitability solution: 0.01 mg/mL of USP Urea Related Compound A RS and 10 mg/mL of USP Urea RS in Diluent

Standard solution: 5 mg/mL of USP Urea RS in Diluent

Sample solution: 5 mg/mL of Urea in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 195 nm

Column: 15-cm × 4.6-mm; 2.7-µm packing L86

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 2 µL

System suitability

Sample: System suitability solution

[Note—The relative retention times for urea related compound A and urea are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between urea related compound A and urea

Relative standard deviation: NMT 1.0% for urea

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of urea (CH₄N₂O) in the portion of Urea 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 Urea RS in the Standard solution (mg/mL)

C_u = concentration of Urea in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.01 mg/mL of USP Urea Related Compound A RS and 10 mg/mL of USP Urea RS in Diluent

Standard solution: 0.01 mg/mL of USP Urea RS and 0.01 mg/mL of USP Urea Related Compound A RS in Diluent

Sample solution: 10 mg/mL of Urea in Diluent

System suitability

Sample: System suitability solution

[Note—For the relative retention times, see Table 2.]

Suitability requirements

Resolution: NLT 1.5 between urea and urea related compound A

Relative standard deviation: NMT 1.0% for urea

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of urea related compound A in the portion of Urea taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of urea related compound A from the Sample solution

r_s = peak response of urea related compound A from the Standard solution

C_s = concentration of USP Urea Related Compound A RS in the Standard solution (mg/mL)

C_u = concentration of Urea in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecied impurity in the portion of Urea taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of any impurity from the Sample solution

r_s = peak response of urea from the Standard solution

C_s = concentration of USP Urea RS in the Standard solution

C_u = concentration of Urea in the Sample solution

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

5 SPECIFIC TESTS

Change to read:

Alcohol-Insoluble Matter

Sample solution: Dissolve 5.0 g of Urea in 50 mL of warm alcohol. _{(ERR 1-Nov-2023)}

Analysis: If any insoluble residue remains, pass the Sample solution through a tared lter, wash the residue and the lter with 20 mL of warm alcohol _{(ERR 1-Nov-2023)} , and dry at 105° for 1 h.

Acceptance criteria: NMT 2 mg (0.04%)

Sterility Tests 〈71〉: Where the label states that Urea is sterile, it meets the requirements.

Bacterial Endotoxins Test 〈85〉: Where the label states that Urea must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.003 USP Endotoxin Units/mg of urea.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at 25°, excursions permitted between 15° and 30°.

Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.

USP Reference Standards 〈11〉

USP Urea RS

USP Urea Related Compound A RS

Dicarbonimidic diamide.

C₂H₅N₃O₈      103.08