Tetrahydrozoline Hydrochloride Ophthalmic Solution

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 Ophthalmic Solution is a sterile, isotonic solution of Tetrahydrozoline Hydrochloride in water. It contains NLT 90.0% and NMT 110.0% of the labeled amount of tetrahydrozoline hydrochloride (C₁₃H₁₆N₂ · HCl).

2 IDENTIFICATION

Change to read:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- May-2022)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Solution A: 20 mM dibasic ammonium phosphate in water. Adjust with ammonium hy droxide to a pH of 9.0.

Mobile phase: Acetonitrile and Solution A (15:85)

Standard solution: 0.025 mg/mL of USP Tetrahydrozoline Hydrochloride RS in water

Sample solution: Nominally 0.025 mg/mL of tetrahydrozoline hydrochloride prepared as follows. Transfer a suitable volume of Ophthalmic Solution to a suitable volumetric flask. Dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identification A, use a diode array detector in the range of 195–400 nm. (USP 1-May-2022)

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

Column temperature: 37°

Flow rate: 1.2 mL/min Injection volume: 25 µL

Run time: NLT 2 times the retention time of tetrahydrozoline

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.8–2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tetrahydrozoline hydrochloride (C₁₃H₁₆N₂ · HCl) in the portion of Ophthalmic Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of tetrahydrozoline from the Sample solution

r_S = peak response of tetrahydrozoline from the Standard solution

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

C_U = nominal concentration of tetrahydrozoline hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A: 20 mM dibasic ammonium phosphate in water. Adjust with ammonium hy droxide to a pH of 9.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 250 µg/mL of USP Tetrahydrozoline Hydrochloride RS and 5 µg/mL each of USP Tetrahydrozoline Related Compound A RS, USP Tetrahy drozoline Related Compound C RS, and USP Tetrahy drozoline Related Compound E RS in water (USP 1-May-2022)

Standard solution: 5 µg/mL of USP Tetrahy drozoline Hy drochloride RS (USP 1-May-2022) in water

Sensitivity solution: 0.25 µg/mL of USP Tetrahydrozoline Hydrochloride RS in water, from the Standard solution

Sample solution: Nominally 250 µg/mL of tetrahydrozoline hydrochloride in water prepared as follows. Transfer a suitable volume of Ophthalmic Solution to a suitable volumetric flask. Dilute with water to volume and mix.

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: 50 µL

System suitability

Samples: Standard solution and Sensitivity solution [NOTE—See Table 2 for the relative retention times.]

Suitability requirements

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 specified and any unspecified degradation product in the portion of Ophthalmic Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each specified and any unspecified degradation product from the Sample solution

r_S = peak response of tetrahydrozoline from the Standard solution

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

C_U = nominal concentration of tetrahydrozoline hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.1%. (USP 1-May-2022)

Table 2

^a Methyl 1,2,3,4-tetrahydronaphthalene-1-carboxylate.

5 SPECIFIC TESTS

STERILITY TESTS 〈71〉: Meets the requirements

PH 〈791〉: 5.8–6.5

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

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

C₁₁H₁₂O₂    176.22

USP Tetrahydrozoline Related Compound

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

C₁₃H₁₈N₂O    218.30 (USP 1-May-2022)