Xylometazoline 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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C₁₆H₂₄N₂ · HCl     280.84

1H-Imidazole, 2-[[4-(1,1-dimethylethyl)-2,6-dimethylphenyl]methyl]-4,5-dihydro-, monohydrochloride; 2-(4-tert-Butyl-2,6-dimethylbenzyl)-2-imidazoline monohydrochloride CAS RN: 1218-35-5; UNII: X5S84033NZ.

1 DEFINITION

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Xylometazoline Hydrochloride contains NLT 98.0% and NMT 102.0% _{(USP 1-Aug-2019)} of xylometazoline hydrochloride (C₁₆H₂₄N₂ · HCl), calculated on the dried basis.

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{(CN 1-May-2020)}, (197K), or (1974) _{(USP 1-A00-2019)}

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B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-Aug-2019)}

Add the following:

C. IDENTIFICATION TESTS GENERAL (191), Chemical Identification Tests, Chloride

Sample solution: 5 mg/mL of Xylometazoline Hydrochloride in water

Acceptance criteria: Meets the requirements of the silver nitrate precipitate test _{(USP 1-Aug-2019)}

3 ASSAY

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PROCEDURE

Solution A: 1.4 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.02 mg/mL each of USP Xylometazoline Hydrochloride RS and USP Xylometazoline Related Compound A RS in water

Standard solution: 0.1 mg/mL of USP Xylometazoline Hydrochloride RS in water

Sample solution: 0.1 mg/mL of Xylometazoline Hydrochloride in water

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 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times are given in Table 2.]

Suitability requirements

Resolution: NLT 2.0 between xylometazoline related compound A and xylometazoline, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of xylometazoline hydrochloride (C₁₆H₂₄N₂ · HCl) in the portion of Xylometazoline Hydrochloride taken:

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

r_u = peak response of xylometazoline from the Sample solution

r_s = peak response of xylometazoline from the Standard solution

C_s = concentration of USP Xylometazoline Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0% on the dried basis _{(USP 1-Aug-2019)}

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

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ORGANIC IMPURITIES

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

Sensitivity solution: 0.5 µg/mL of USP Xylometazoline Hydrochloride RS in water

Standard solution: 0.002 mg/mL of USP Xylometazoline Hydrochloride RS in water

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

System suitability

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

[NOTE-The relative retention times are given in Table 2.]

Suitability requirements

Resolution: NLT 2.0 between xylometazoline related compound A and xylometazoline, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Xylometazoline Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of xylometazoline from the Standard solution

C_s = concentration of USP Xylometazoline Hydrochloride RS in the Standard solution (mg/mL)

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

F = relative response factor for the corresponding impurity (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

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pH 〈791〉

Sample solution: 50 mg/mL of Xylometazoline Hydrochloride in water

Acceptance criteria: 5.0–6.6 _{(USP 1-Aug-2019)}

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Change to read:

USP Reference Standards 〈11〉

USP Xylometazoline Hydrochloride RS

USP Xylometazoline Related Compound A RS

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

C₁₆H₂₆N₂O   262.39 _{(USP 1-Aug-2019)}