Tetracaine Hydrochloride for Injection

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

Tetracaine Hydrochloride for Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of tetracaine hydrochloride (C₁₅H₂₄N₂O₂ ·HCl).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: The Sample solution from the Assay.

Acceptance criteria: Meets the requirements

B.

Sample solution: 100 mg in 10 mL of water

Analysis: To the Sample solution add 1 mL of potassium thiocyanate solution (1 in 4). A crystalline precipitate is formed. Recrystallize the precipitate from water, and dry at 80° for 2 h.

Acceptance criteria: The crystalline precipitate melts between 130° and 132°.

3 ASSAY

Procedure

Buffer: Buffer B.6 (see Antibiotics—Microbial Assays 〈81〉, Media and Solutions, Solutions, Buffers,Table 12)

Diluent: Dilute hydrochloric acid (1 in 200)

Standard stock solution: 0.2 mg/mL of USP Tetracaine Hydrochloride RS in water

Standard solution: 0.01 mg/mL of USP Tetracaine Hydrochloride RS prepared as follows. Pipet 5 mL of the Standard stock solution into a 100-mL volumetric flask, add 5 mL of Diluent and 10 mL of Buffer, and dilute with water to volume.

Sample stock solution: Nominally 0.2 mg/mL of tetracaine hydrochloride in water prepared as follows. Transfer to a tared 20-mL beaker the contents of a sufficient number of containers of Tetracaine Hydrochloride for Injection to yield about 100 mg of tetracaine hydrochloride.

Weigh immediately, and transfer with the aid of water to a 500-mL volumetric flask. Dilute with water to volume.

Sample solution: Nominally 0.01 mg/mL of tetracaine hydrochloride prepared as follows. Transfer 5.0 mL of the Sample stock solution to a 100-mL volumetric flask, add 5 mL of Diluent and 10 mL of Buffer, then dilute with water to volume.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 310 nm

Blank: Water

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of labeled amount of tetracaine hydrochloride in the portion of Tetracaine Hydrochloride for

Injection taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Uniformity of Dosage Units 〈905〉: Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Buffer: Buffer B.6 (see Antibiotics—Microbial Assays 〈81〉, Media and Solutions, Solutions, Buffers,Table 12)

Diluent: Dilute hydrochloric acid (1 in 200)

Standard stock solution: 0.2 mg/mL of USP Tetracaine Hydrochloride RS in water

Standard solution: 0.01 mg/mL of USP Tetracaine Hydrochloride RS prepared as follows. Transfer 5 mL of the Standard stock solution into a 100-mL volumetric flask, add 5 mL of Diluent and 10 mL of Buffer, and dilute with water to volume.

Sample stock solution: Transfer the contents of one container, with the aid of water, to a 200-mL volumetric flask, and add water to volume.

Sample solution: Nominally 0.01 mg/mL of tetracaine hydrochloride from the Sample stock solution prepared as follows. Pipet a portion of the Sample stock solution, equivalent to 1 mg of tetracaine hydrochloride, to a 100-mL volumetric flask, add 5 mL of Diluent and 10 mL of

Buffer, and dilute with water to volume.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tetracaine hydrochloride in each container taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

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

(CN 1-Aug-2023)

5 IMPURITIES

Residue on Ignition

Sample: 500 mg

Analysis: Transfer the Sample to a beaker, and dissolve in 10 mL of methanol. Filter through paper previously washed with methanol, collecting the filtrate in an ignited and tared crucible, and wash the beaker and the filter paper with 25–30 mL of methanol. Evaporate with the aid of heat and a current of air to dryness, and proceed as directed in Residue on Ignition 〈281〉, beginning with “Heat gently at a temperature as low as practicable”.

Acceptance criteria: NMT 0.1%

Organic Impurities

Standard solution: 0.2 mg/mL of 4-(butylamino) benzoic acid in methanol

Sample solution: 50 mg/mL of Tetracaine Hydrochloride for Injection in water

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 5 μL

Developing solvent system: Chloroform, methanol, and isopropylamine (98:7:2)

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter. Develop the plate in a suitable chromatographic chamber containing the Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, and dry in a current of warm air. Examine the plate under short-wavelength UV light.

Acceptance criteria: Any spot from the Sample solution, other than the principal spot, is not more intense than the principal spot from the Standard solution (0.4%), and the sum of the intensities of any such spots is not greater than 0.8%.

6 SPECIFIC TESTS

pH 〈791〉: 5.0–6.0 in a solution (1 in 100)

Water Determination 〈921〉, Method I: NMT 2.0%

Bacterial Endotoxins Test 〈85〉: NMT 0.7 USP Endotoxin Units/mg of tetracaine hydrochloride

Completeness of Solution 〈641〉

Sample: Nominally 10 mg of tetracaine hydrochloride

Acceptance criteria: The Sample dissolves in 1 mL of water in NMT 2 s to yield a colorless solution free from undissolved solid.

Constituted Solution: At the time of use, it meets the requirements in Injections and Implanted Drug Products, 〈1〉, Specific Tests, Completeness and clarity of solutions.

Sterility Tests 〈71〉: Meets the requirements

Other Requirements: It meets the requirements in Labeling 〈7〉, Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for constitution, preferably Type I glass.

USP Reference Standards 〈11〉

USP Tetracaine Hydrochloride RS