Benzocaine Topical Aerosol

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

Benzocaine Topical Aerosol is a solution of Benzocaine in a pressurized container. It contains NLT 90.0% and NMT 110.0% of the labeled amount of benzocaine (C₉H₁₁NO₂).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

Procedure

Solution A: 0.1% Trifluoroacetic acid, prepared by diluting 1.0 mL of trifluoroacetic acid with water to 1 L

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Solution A and Solution B (1:1)

System suitability solution: 1 µg/mL each of USP Benzocaine RS, USP Aminobenzoic Acid RS, and USP Ethyl 4-Nitrobenzoate RS in Diluent

Standard solution: 0.1 mg/mL of USP Benzocaine RS in Diluent

Sample composite: Spray a portion of Topical Aerosol into a beaker or glass tube, and heat on a steam bath or a heating module at 100° for a few minutes to expel residual propellant. Use the resulting benzocaine solution.

Sample solution: Nominally 0.1 mg/mL of benzocaine in Diluent prepared as follows. Transfer a known quantity of benzocaine solution from a portion of Sample composite to an appropriate volumetric flask, dissolve, and dilute with Diluent to volume.

Chromatographic system

Mode: LC

Detector: UV 280 nm. For Identification test A, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 6 between aminobenzoic acid and benzocaine; NLT 6 between benzocaine and ethyl 4-nitrobenzoate, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzocaine (C₉H₁₁NO₂) in the portion of Topical Aerosol taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of benzocaine from the Sample solution

rₛ = peak response of benzocaine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

Organic Impurities

Solution A: 0.1% Trifluoroacetic acid, prepared by diluting 1.0 mL of trifluoroacetic acid with water to 1 L

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Solution A and Solution B (1:1)

Standard solution: 1 µg/mL each of USP Benzocaine RS, USP Aminobenzoic Acid RS, and USP Ethyl 4-Nitrobenzoate RS in Diluent

Sample composite: Spray a portion of the Topical Aerosol into a beaker or glass tube, and heat on a steam bath or a heating module at 100° for a few minutes to expel residual propellant. Use the resulting benzocaine solution.

Sample solution: Nominally 0.5 mg/mL of benzocaine in Diluent prepared as follows. Transfer 50 mg of benzocaine from a portion of Sample composite to a 100-mL volumetric flask, dissolve, and dilute with Diluent to volume.

Chromatographic system

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 6 between aminobenzoic acid and benzocaine; NLT 6 between benzocaine and ethyl 4-nitrobenzoate

Relative standard deviation: NMT 3% for each peak corresponding to benzocaine, aminobenzoic acid, and ethyl 4-nitrobenzoate

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of aminobenzoic acid and ethyl 4-nitrobenzoate in the portion of Topical Aerosol taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of aminobenzoic acid or ethyl 4-nitrobenzoate from the Sample solution

rₛ = peak response of aminobenzoic acid or ethyl 4-nitrobenzoate from the Standard solution

Cₛ = concentration of USP Aminobenzoic Acid RS or USP Ethyl 4-Nitrobenzoate RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual, unspecified impurity in the portion of Topical Aerosol taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any other individual, unspecified impurity from the Sample solution

rₛ = peak response of benzocaine from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%.

5 SPECIFIC TESTS

Topical Aerosols, Pressure Test 〈603〉: Meets the requirements

Leak Rate 〈604〉: Meets the requirements

Minimum Fill 〈755〉: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in pressurized containers, and avoid exposure to excessive heat.

USP Reference Standards 〈11〉

USP Aminobenzoic Acid RS

Benzoic acid, 4-amino. C₇H₇NO₂ 137.14

USP Benzocaine RS

USP Ethyl 4-Nitrobenzoate RS

Benzoic acid, 4-nitro-, ethyl ester. C₉H₉NO₄ 195.17