Oxymetazoline 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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C₁₆H₂₄N₂O · HCl 296.84

Phenol, 3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)-2,4-dimethyl-, monohydrochloride;

6-tert-Butyl-3-(2-imidazolin-2-ylmethyl)-2,4-dimethylphenol monohydrochloride CAS RN®: 2315-02-8.

1 DEFINITION

Oxymetazoline Hydrochloride contains NLT 98.5% and NMT 101.5% of oxymetazoline hydrochloride (C₁₆H₂₄N₂O · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (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: 50 mg in 3 mL of water

Analysis: To the Sample solution add 1 mL of 6 N ammonium hydroxide. Filter, and acidify the filtrate with nitric acid. Acceptance criteria: The filtrate meets the requirements.

3 ASSAY

Procedure

Mobile phase: Methanol, 1 M sodium acetate, glacial acetic acid, and water (40:10:4:46)

Standard solution: 0.5 mg/mL of USP Oxymetazoline Hydrochloride RS in Mobile phase

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

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; packing L9

Flow rate: 1 mL/min

Injection volume: 20 µL

3.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.55% for ve replicate injections

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxymetazoline hydrochloride (C₁₆H₂₄N₂O · HCl) in the portion of Oxymetazoline 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 Oxymetazoline Hydrochloride RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer: 1.36 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: See Table 1. Return to the original conditions, and re-equilibrate the system.

Table 1

System suitability solution: 1.0 mg/mL of USP Oxymetazoline Hydrochloride RS and 1.5 µg/mL of USP Oxymetazoline Related Compound A RS in water

Standard solution: 1.0 µg/mL of USP Oxymetazoline Hydrochloride RS and 1.5 µg/mL of USP Oxymetazoline Related Compound A RS in water

Sample solution: 1.0 mg/mL of Oxymetazoline Hydrochloride in water

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 10 µL

4.2 System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between oxymetazoline related compound A and oxymetazoline peaks

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxymetazoline related compound A in the portion of Oxymetazoline Hydrochloride taken:

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

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

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

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

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

Calculate the percentage of each individual unspecified impurity in the portion of Oxymetazoline Hydrochloride taken:

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

r_U = peak response of each individual unspecified impurity from the Sample solution

r_S = peak response of oxymetazoline from the Standard solution

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

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

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

Table 2

a N-(2-Aminoethyl)-2-[4-(tert-butyl)-3-hydroxy-2,6-dimethylphenyl]acetamide.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 50 mg/mL in water

Acceptance criteria: 4.0–6.5

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Oxymetazoline Hydrochloride RS

USP Oxymetazoline Related Compound A RS

N-(2-Aminoethyl)-2-[4-(tert-butyl)-3-hydroxy-2,6-dimethylphenyl]acetamide hydrochloride.

C₁₆H₂₆N₂O₂ ·  HCl             314.85