Naphazoline 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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C₁₄H₁₄N₂ · HCI           246.74

1H-Imidazole, 4,5-dihydro-2-(1-naphthalenylmethyl)-, monohydrochloride;

2-(1-Naphthylmethyl)-2-imidazoline monohydrochloride   CAS RN^®: 550-99-2; UNII: MZ1131787D.

1 DEFINITION

Naphazoline Hydrochloride contains NLT 98.0% and NMT 102.0% of naphazoline hydrochloride (C₁₄H₁₄N₂ · HCI), 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.

C. IDENTIFICATION TESTS GENERAL, Chloride (191),

Sample solution: 10 mg/mL in water

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: In a 1000-mL volumetric flask, dissolve 3.0 g of monobasic potassium phosphate in 800 mL of water. Add 3.0 mL of triethylamine, adjust with phosphoric acid to a pH of 3.0, and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (20:80)

Chromatographic system

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of naphazoline hydrochloride (C₁₄H₁₄N₂ · HCI) in the portion of Naphazoline Hydrochloride 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 Naphazoline Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Naphazoline Hydrochloride 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 0.2%

4.2 ORGANIC IMPURITIES

Solution A: Acetonitrile, glacial acetic acid, and water (30:0.5:70)

Mobile phase: 1.1 g/L of anhydrous sodium 1-octanesulfonate in Solution A

System suitability solution: 0.025 mg/mL of USP Naphazoline Hydrochloride RS and 0.05 mg/mL of 1-naphthylacetic acid in Mobile phase

Standard solution: 0.5 µg/mL each of USP Naphazoline Hydrochloride RS and USP Naphazoline Related Compound A RS in Mobile phase

Sample solution: 0.5 mg/mL of Naphazoline Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm x 25-cm; 3-µm or 5-µm packing L7

Flow rate: 1 mL/min

Injection volume: 20 µL.

Run time: NLT 3 times the retention time of the naphazoline peak

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 5.0 between the naphazoline and 1-naphthylacetic acid peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of naphazoline related compound A in the portion of Naphazoline Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of naphazoline related compound A from the Sample solution

r_S = peak response of naphazoline related compound A from the Standard solution

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

C_U = concentration of Naphazoline Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Naphazoline Hydrochloride 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 naphazoline from the Standard solution 

C_S = concentration of USP Naphazoline Hydrochloride RS in the Standard solution (mg/mL) 

C_U = concentration of Naphazoline Hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria

Individual impurities: See Table 1. Disregard any impurity peaks less than 0.05%.

Table 1

5 SPECIFIC TESTS

5.1 PH (791)

Sample solution: 10 mg/mL in carbon dioxide-free water

Acceptance criteria: 5.0-6.6. The Sample solution is clear and colorless.

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

USP REFERENCE STANDARDS (11)

USP Naphazoline Hydrochloride RS

USP Naphazoline Related Compound A 85

N-(2-Aminoethyl)-2-(naphthalen-1-yl)acetamide.

C₁₄H₁₆N₂O       228.29