Arginine

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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C₆H₁₄N₄O₂  174.20

L-arginine CAS RN^®: 74-79-3.

1 DEFINITION

Arginine contains NLT 98.5% and NMT 101.5% of C₆H₁₄N₄O₂, as L-arginine, calculated on the dried basis.

2 IDENTIFICATION

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

3 ASSAY

3.1 PROCEDURE

Sample: 80 mg of Arginine

Titrimetric system (See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Potentiometric

Blank: 3 mL of formic acid and 50 mL of glacial acetic acid

Analysis: Dissolve the Sample in a mixture of 3 mL of formic acid and 50 mL of glacial acetic acid, and titrate with Titrant. Calculate the percentage of C₆H₁₄N₄O₂ in the portion taken:

Result = [(V - B) x N x F x 100]/W

V = Sample titrant volume (mL)

B = Blank titrant volume (mL)

N = titrant normality (mEq/mL)

F = equivalency factor: 87.10 mg/mEq

W = weight of Sample (mg)

Acceptance criteria: 98.5%-101.5% on the dried basis

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.3%

CHLORIDE AND SULFATE, Chloride (221): A 1.0-g portion shows no more chloride than corresponds to 0.70 mL of 0.020 N hydrochloric acid (0.05%).

CHLORIDE AND SULFATE, Sulfate (221): A 1.0-g portion shows no more sulfate than corresponds to 0.30 mL of 0.020 N sulfuric acid (0.03%).

Change to read:

IRON (241), Procedures, Procedure 1 (CN 1-JUN-2023): NMT 30 ppm

4.2 ORGANIC IMPURITIES

4.2.1 PROCEDURE

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Standard solution: 0.05 mg/mL of USP L-Arginine RS in 0.1 N hydrochloric acid. [NOTE-This solution has a concentration equivalent to 0.5% of that of the Sample solution.]

Sample solution: 10 mg/mL of Arginine in 2 N hydrochloric acid

System suitability solution: 0.4 mg/mL each of USP L-Arginine RS and USP L-Lysine Hydrochloride RS in 0.1 N hydrochloric acid

Spray reagent: 2 mg/mL of ninhydrin in a mixture of butyl alcohol and 2 N acetic acid (95:5)

Application volume: 5 µL

Developing solvent system: Isopropyl alcohol and ammonium hydroxide (7:3)

Analysis

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

Proceed as directed under Chromatography (621), Thin-Layer Chromatography. Dry the plate between 100° and 105° until the ammonia disappears completely. Spray with Spray reagent, and heat between 100° and 105° for about 15 min. Examine the plate under white light. The chromatogram obtained from the System suitability solution exhibits two clearly separated spots.

Acceptance criteria

Individual impurities: Any secondary spot from the Sample solution is not larger or more intense than the principal spot from the Standard

solution, NMT 0.5%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

OPTICAL ROTATION, Specific Rotation(781S): +26.3° to +27.7°

Sample solution: 80 mg/mL in 6 N hydrochloric acid

LOSS ON DRYING (731): Dry a sample at 105° for 3 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP L-Arginine RS

USPL-Lysine Hydrochloride RS