Arginine Hydrochloride

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.HCI  210.66

L-arginine monohydrochloride;

L-(+)-Arginine monohydrochloride CAS RN^®: 1119-34-2; UNII: F7LTH1E20Y.

1 DEFINITION

Arginine Hydrochloride contains NLT 98.5% and NMT 101.5% of arginine hydrochloride (C₆H₁₄N₄O₂.HCI), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

3 ASSAY

3.1 PROCEDURE

Sample: 100 mg of Arginine Hydrochloride

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Potentiometric

Blank: 50 mL of glacial acetic acid and 3 mL of 98% formic acid. Add 6 mL of mercuric acetate TS.

Analysis: Dissolve the Sample in 3 mL of 98% formic acid and 50 mL of glacial acetic acid. Add 6 mL of mercuric acetate TS and titrate with the Titrant.

Calculate the percentage of arginine hydrochloride (C₆H₁₄N₄O₂.HCI) in the Sample 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, 105.3 mg/mEq

W = weight of Sample (mg)

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 CHLORIDE AND SULFATE, Sulfate (221)

 A 1.6-g portion shows no more sulfate than corresponds to 0.50 mL of 0.020 N sulfuric acid (0.03%).

4.3 CHROMATOGRAPHIC PURITY

System suitability solution: 0.4 mg/mL each of USP Arginine Hydrochloride RS and USP L-Lysine Hydrochloride RS in water

Standard solution: 0.05 mg/mL of USP Arginine Hydrochloride RS in water. [NOTE-This solution has a concentration equivalent to about 0.5% of that of the Sample solution.]

Sample solution: 10 mg/mL of Arginine Hydrochloride in water

Chromatographic system

(See Chromatography (621), Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 5 µL

Developing solvent system: Isopropyl alcohol and ammonium hydroxide (70:30)

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

Analysis

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

Acceptance criteria: Any secondary spot from the Sample solution is not larger or more intense than the principal spot from the Standard solution.

Proceed as directed in the chapter. 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 System suitability solution exhibits two clearly separated spots. OPTICAL ROTATION, Specific Rotation(781S): +21.4° to +23.6° (t = 20 deg)

Individual impurities: NMT 0.5%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation(781S)

+21.4° to +23.6° (t = 20 deg)

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

5.2 LOSS ON DRYING (731)

Dry a sample at 105° for 2 h: it loses NMT 0.2% of its weight.

5.3 CHLORIDE CONTENT

Sample: 350 mg of Arginine Hydrochloride

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS

Endpoint detection: Colorimetric

Analysis: Transfer the Sample to a porcelain casserole, and add 140 mL of water and 1 mL of dichlorofluorescein TS. Mix and titrate with the Titrant until the silver chloride flocculates and the mixture acquires a faint pink color.

Calculate the percentage of chloride (CI) in the Sample taken:

Result = (V x N x F x 100)/W

V = Sample titrant volume (mL)

N = titrant normality (mEq/mL)

F = equivalency factor, 35.45 mg/mEq

W = weight of Sample (mg)

Acceptance criteria: 16.5%-17.1%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Arginine Hydrochloride RS

USP L-Lysine Hydrochloride RS