Tetrahydrozoline 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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1 DEFINITION

Tetrahydrozoline Hydrochloride contains NLT 98.0% and NMT 102.0% of tetrahydrozoline hydrochloride (C₁₃H₁₆N₂ · HCl), calculated on the dried

basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197A or 197K

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 〈191〉 , Chemical Identification Tests, Chloride Sample solution: 5 mg/mL

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: 2.64 g/L of dibasic ammonium phosphate in water; adjusted with ammonium hy droxide to a pH of 9.0

Mobile phase: Acetonitrile and Buffer (15:85)

Standard solution: 0.025 mg/mL of USP Tetrahy drozoline Hy drochloride RS in water

Sample solution: 0.025 mg/mL of Tetrahydrozoline Hydrochloride in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

Column temperature: 37°

Flow rate: 1.2 mL/min

Injection volume: 25 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 tetrahydrozoline hydrochloride (C₁₃H₁₆N₂ · HCl) in the portion of Tetrahydrozoline Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%

Change to read:

ORGANIC IMPURITIES

Buffer: Dissolve 4 g of sodium dodecyl sulfate in 600 mL water. Add 3 mL of triethylamine and adjust with orthophosphoric acid to a pH of 2.0.

Mobile phase: Methanol, acetonitrile, and Buffer (26.5: 26.5: 47)

System suitability solution: 2 mg/mL of USP Tetrahy drozoline Hy drochloride RS, and 2 µg/mL each of USP Tetrahy drozoline Related Compound A RS, USP Tetrahydrozoline Related Compound B RS, USP Tetrahydrozoline Related Compound C RS, USP Tetrahydrozoline Related Compound D RS, and USP Tetrahy drozoline Related Compound E RS in Mobile phase

Standard solution: 2 µg/mL of USP Tetrahydrozoline Hydrochloride RS in Mobile phase

Sensitivity solution: 1 µg/mL of USP Tetrahy drozoline Hy drochloride RS in Mobile phase from the Standard solution Sample solution: 2 mg/mL of Tetrahydrozoline Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 4-µm packing L87

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 3 times the retention time of tetrahydrozoline

System suitability

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

Suitability requirements

Resolution: NLT 1.5 between tetrahydrozoline and tetrahydrozoline related compound B, System suitability 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 any individual impurity in the portion of Tetrahydrozoline Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of any individual impurity from the Sample solution

r_S = peak response of tetrahydrozoline from the Standard solution

C_S = concentration of USP Tetrahy drozoline Hy drochloride RS in the Standard solution (µg/mL)

C_U = concentration of Tetrahydrozoline Hydrochloride in the Sample solution (µg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

^a 2-(Naphthalen-1-yl)-4,5-dihydro-1H-imidazole.

(USP 1-May-2022)

5 SPECIFIC TESTS

LOSS ON DRYING 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature. Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Tetrahydrozoline Hydrochloride RS

USP Tetrahydrozoline Related Compound A RS

1,2,3,4-Tetrahydronaphthalene-1-carbonitrile.

C₁₁H₁₁N    157.21

USP Tetrahydrozoline Related Compound B RS

2-(1,2,3,4-Tetrahydronaphthalen-1-yl)-1H-imidazole.

C₁₃H₁₄N₂       198.27

USP Tetrahydrozoline Related Compound C RS

1,2,3,4-Tetrahydronaphthalene-1-carboxylic  acid.

C₁₁N₁₂O₂        176.22

USP Tetrahydrozoline Related Compound D RS

2-(Naphthalen-1-yl)-4,5-dihydro-1H-imidazole  hydrochloride.

C₁₃H₁₂N₂ · HCl     232.71

USP Tetrahydrozoline Related Compound E RS

N-(2-Aminoethyl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide.

C₁₃H₁₈N₂O    218.30 (USP 1-May-2022)