Proparacaine 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

Proparacaine Hydrochloride Ophthalmic Solution is a sterile, aqueous solution of Proparacaine Hydrochloride. It contains NLT 95.0% and NMT 110.0% of the labeled amount of proparacaine hydrochloride (C₁₆H₂₆N₂O₃ · HCl).

2 IDENTIFICATION

A.

Solution A: Dilute hydrochloric acid (1 in 100)

Solution B: 100 mg/mL of sodium nitrite

Solution C: 20 mg/mL of 2-naphthol in 1 N sodium hydroxide

Sample solution: 1 mL of Ophthalmic Solution

Analysis 1: To the Sample solution in a test tube add 5 mL of Solution A, mix, and cool in an ice bath for 2 min. Add 2 drops of Solution B, stir, and cool again for 2 min. Add 1 mL of Solution C.

Acceptance criteria 1: A scarlet-red precipitate is formed.

Analysis 2: Add 5 mL of acetone to the test tube contents of Analysis 1.

Acceptance criteria 2: The precipitate does not dissolve.

3 ASSAY

Procedure

Buffer: 6.8 g/L of monobasic potassium phosphate. Add 5 mL of triethylamine, and adjust with 5 N potassium hydroxide to a pH of 7.5. Pass through a filter of 0.5-µm or finer pore size, and degas.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard stock solution: 1 mg/mL of USP Proparacaine Hydrochloride RS

Standard solution: 0.1 mg/mL of USP Proparacaine Hydrochloride RS in Mobile phase from the Standard stock solution. Use this solution within 6 h.

Sample solution: Nominally equivalent to 0.1 mg/mL of proparacaine hydrochloride from a measured volume of Ophthalmic Solution in Mobile phase. Use this solution within 6 h.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 270 nm

Column: 4.6-mm × 15-cm; 5-µm spherical packing L10

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 3000 theoretical plates

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of proparacaine hydrochloride (C₁₆H₂₆N₂O₃ · HCl) in the portion of Ophthalmic Solution taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak area from the Sample solution

rₛ = peak area from the Standard solution

Cₛ = concentration of USP Proparacaine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of proparacaine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–110.0%

4 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉: 3.5–6.0

5 ADDITIONAL REQUIREMENTS

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

Labeling: Label it to indicate that it is to be stored in a refrigerator after the container is opened.

USP Reference Standards 〈11〉

USP Proparacaine Hydrochloride RS